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Biomedical subjects

M Liguori

Publications and source records attributed to M Liguori.

At least 19 recordsLinked to original sources
PubMed2007

Investigating the role of brain-derived neurotrophic factor in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a common, heterogeneous disorder of the central nervous system with a complex trait composed of both genetic and environmental factors. Recently, scientific interest has increased in defining factors that possibly contribute to brain functional plasticity; the results might be useful to assess the relationship between MS lesion burden and clinical events, as well as explaining the well-known phenotypic heterogeneity of the disease. In this study, we explored the effect of the Val66Met brain-derived neurotrophic factor (BDNF) functional polymorphism on cognitive performances and volumetric measurements obtained by magnetic resonance imaging of the brain in a selected population of relapsing-remitting MS (RRMS) patients, with relatively short disease duration and minimal clinical disability, compared to gender, age and educational-level matched healthy subjects. We found that in the RRMS group, the BDNF Met-allele was significantly associated with the lower volume of cerebral grey matter (GM) (P = 0.005). Furthermore, a significant (P = 0.013) interaction effect between 'MS-status' and the BDNF genotype was found for GM volumes, with the result that patients carrying the BDNF Met-allele showed a higher risk of developing global GM atrophy than the homozygous Val/Val. No BDNF-related impact on global neuropsychological functions resulted in either RRMS patients or controls. Our data seem to be consistent with the reported influence of BDNF in neuronal plasticity, thus suggesting that the Met-allele might have a negative prognostic effect on cortical morphometry in RRMS patients.

Adolescent↗
PubMed2006

Genetic variation in the myeloperoxidase gene and cognitive impairment in multiple sclerosis.

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to beta-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS.

Alleles↗
PubMed2006

Low specificity of anti-tissue transglutaminase antibodies in patients with primary biliary cirrhosis.

The association between celiac disease (CD) and primary biliary cirrhosis (PBC) is well documented in medical literature; however, a high frequency of false positive results of the anti-transglutaminase (anti-tTG) test has been reported in patients with PBC. To verify if the positive results for anti-tTG autoantibody are false positives due to cross reactivity with mitochondrial antigens, we studied 105 adult patients affected with PBC, positive for anti-mitochondrial M2 antibodies. Anti-tTG IgA antibodies were studied by using six different immunoenzymatic assays that employ the tTG antigen obtained from different sources (human recombinant, placenta, red blood cells, and guinea pig liver). On the whole, 28 out of 105 PBC subjects tested positive for anti-tTG IgA antibodies, but only two were eventually found to be affected by CD; the other 26 were shown to be false positive. The specificity of the various antigenic substrates ranged from 88.5% of the human erythrocytes tTG to 97.1% of the human recombinant tTG. The results of this study showed that a true association between PBC and CD was present in only 2% of the patients and that, in most cases, the false positive results were attributable to the type of substrate utilized in the assay.

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↗
PubMed2004

A novel mutation (Thr116Ile) in the presenilin 1 gene in a patient with early-onset Alzheimer's disease.

We report a novel presenilin 1 (PSN1) mutation (Thr116Ile) in a woman with early onset Alzheimer's disease (AD). This mutation was not found in 100 healthy controls, indicating that this is not a common polymorphism. The patient presented with forgetfulness at age 45, followed over the next 3 years by a worsening of the memory loss and frequent episodes of confusion and spatial disorientation. Neuroimaging studies were consistent with AD. The analysis of the family's pedigree showed that the proband was apparently the only member affected. Because the early death of several close relatives (i.e. the mother and the grandmother) and the demonstration that the father is not a mutation carrier, it is suggested that either a de novo mutation or a censor effect might have occurred. Our finding supports the indication that PSN1 mutations should be searched for in early-onset AD, particularly when a censor effect precludes a precise genetic analysis.

Alzheimer Disease↗
PubMed2004

[Effectiveness of Troxerutin in association with Pycnogenol in the pharmacological treatment of venous insufficiency].

AIM: The purpose of our study was to assess the different effectiveness of Troxerutin in association with Pycnogenol compared to the effects obtainable with the same pharmacological principle in monotherapy in patients suffering from venous insufficiency. METHODS: Seventy patients with venous insufficiency of the lower extremities at the first stages of the CEAP classification (Cs1,3; Es; As 1; invalidity score 2, clinical score 1-2) were selected and subdivided into 2 groups: one of 50 and one of 20. All patients reported the following symptoms either associated or in isolation: heaviness, cramps, pruritus and pain at palpation. Evaluation of the degree of venous insufficiency was carried out by means of echo-Doppler at recruitment. The 1st group received Troxerutin (470 mg) associated with Pycnogenol (20 mg) in a dose of 1 g/day per os for 60 days; the 2nd group Troxerutin alone (300 mg) in a dose of 2 tablets twice a day per os for 60 days. Controls were set up at 30 and 60 days from the start of treatment and after a period of 3 months from the end of treatment to assess the effects on the symptomatology over time. The effectiveness of the drugs on symptomatology reported by both groups was assessed by means of an analysis of the qualitative variation of the symptoms using the score-scales method: 3=severe; 2=moderate; 1=slight; 0=absent and this variation was expressed as a percentage decrease and analysed using Student's test. RESULTS: The results of our study after 30 days of treatment highlighted a clinical improvement in all patients with the disappearance of symptoms (score from 3 to 1) in 50% of patients in the 1st group and in 35% in the 2nd with a peak of 96% in patients of the 1st group and 80% in the 2nd at the end of treatment (60 days). This result held stable in the course of follow-up for 96% of patients in the 1st group (p<0.001) and for 50% of those in the 2nd group (p<0.005). CONCLUSION: Comparison between the 2 groups showed that the group which received Troxerutin associated with Pycnogenol reported greater therapeutic effectiveness than the control group as regards both the rapidity of disappearance of the symptoms and as regards maintenance of the cure obtained.

Adjuvants, Immunologic↗
PubMed2002

Course and prognosis in early-onset MS: comparison with adult-onset forms.

OBJECTIVES: To establish the prognostic role of clinical and demographic factors in a hospital-based cohort of MS patients categorized by age at clinical onset and clinical course. METHODS: Eighty-three patients with MS had a clinical onset of the disease in childhood (age <16 years; early-onset MS [EOMS]) and 710 in adult age (between 16 and 65 years; adult-onset MS [AOMS]). Patients were followed for a mean period of observation of 5 years. Univariate and multivariate analyses of clinical and demographic predictors for rapid progression and disability were performed using a stepwise Cox regression model with time-dependent covariates. RESULTS: In EOMS, the Expanded Disability Status Scale (EDSS) evaluated at last clinical examination was lower than in AOMS, despite a longer disease duration. The probability to reach growth disability and progression was significantly lower in EOMS than in AOMS. Median times to reach EDSS score of 4 and secondary progression were longer in EOMS than in AOMS, but the age at both endpoints was significantly lower in EOMS. In EOMS and AOMS, an irreversible disability was related to a secondary progressive course, a sphincteric system involvement at onset, and an older age at onset (in EOMS only for the group >14 years); in AOMS, other unfavorable factors were a pyramidal involvement at onset and a high relapse frequency in the first 2 years. The risk of entering secondary progression was significantly influenced by a high number of relapses in EOMS and by a higher age at onset and a short interattack interval in AOMS. CONCLUSION: A slower rate of progression of disease characterized EOMS patients, suggesting more plasticity to recover in developing CNS, but the early clinical manifestation cannot be considered a positive prognostic factor.

Adolescent↗
PubMed2002

Prospective study of multiple sclerosis with early onset.

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age > or = 12 years, suggesting a role of hormonal changes in triggering MS onset The mean follow-up duration was 10.9+/-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (+/-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, >6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset age and gender.

Adolescent↗
PubMed2002

Technical procedure and ethical behaviour in biotechnologies of reproduction.

BACKGROUND: The significant and constant progress of biotechnologies applied to sterility and infertility has induced a deeper reflection about bioethical problems. The analysis of only the biological dimension, about the results achieved and desirable future prospects, decreases, leaving out the anthropological dimension. It is therefore necessary to make reference to both the limits of the basic or applied research and to the usual welfare procedure. The aim, that the article sets itself, is to proceed to the bioethical analysis of the most significant topics of artificial insemination and assisted procreation; and it submits to anthropological evaluation the technical aspects, which characterize both the procreation techniques and the research prospects in this area. METHODS: The bioethical analysis, used as a method of study and research, has availed itself of structured reasoning through the evaluation of the scientific, anthropological and legal-deontological dimensions, from an interdisciplinary point of view. The definition of the ethical norm, supported by authors, has been inferred from the analysis of the above-mentioned dimensions, considering the already known bioethical models. In particular, the authors analyse these topics through the model of ontologically based personalism, which suggests, and highlights, ethical norms, both as regards the basic and applied research and as regards usual welfare procedure, in opposition to models like moral sociologism, biologism, moral evolutionism and contractualism. From the beginning we defined "technical procedure" and "ethical behaviour", highlighting the interaction between them. We have made a distinction between artificial insemination, as a substitutive technique, and assisted procreation, as a facilitative technique. In addition through biological and anthropological results we have evaluated the embryo both ontologically and biologically. So we have defined "ontological and biological embryo status". RESULTS AND CONCLUSIONS: The evaluation of the proposed topics for assisted procreation and against artificial insemination, the interaction between technical procedure and ethical behaviour, the acknowledgement of the embryo and personal dignity in every procedure are the principal results and the conclusions that we have arrived at, as regards the bioethical model of ontologically based personalism.

Biotechnology↗
PubMed2001

Axonal damage in multiple sclerosis plaques: a combined magnetic resonance imaging and 1H-magnetic resonance spectroscopy study.

The purpose of this study was to compare magnetic resonance imaging (MRI) features and proton MR spectroscopy (1H-MRS) patterns of multiple sclerosis (MS) plaques in order to define the metabolic substrate in different lesion subtypes. Combined MRI and single-voxel 1H-MRS investigation was performed in 54 MS patients (47 relapsing remitting (RR) and seven secondary progressive (SP)). Sixty-seven MS lesions were selected. Thirty-seven lesions were Gadolinium (Gd) enhancing (nine isointense and 28 hypointense on pre-contrast T(1)-weighted scans) and 30 Gd unenhancing (six isointense and 24 hypointense on pre- and post-contrast T(1)-weighted scans). Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate were evaluated in 1H spectra acquired from MS plaques and from normal white matter (NWM) of 22 neurological controls. MS lesions of RR patients were characterized by a significant increase of Cho/Cr and decrease of NAA/Cr and NAA/Cho ratios. No significant metabolite changes were found in lesions of SP patients. Gd enhancing plaques showed lactate signal with higher frequency (37.8%) than Gd unenhancing plaques (16.7%) (p=0.04). A significant increase of Cho/Cr was found in Gd enhancing lesions when compared to controls (p<0.01), and to Gd unenhancing lesions (p<0.05). In particular, there was evidence of a significant increase of Cho/Cr in pre-contrast T(1) hypointense Gd enhancing lesions (p<0.01 vs. controls). The Gd unenhancing lesions (p<0.01), in particular the T(1) hypointense group (p<0.05), showed a significant decrease of NAA/Cr only when compared to controls. These data confirm that in vivo MRS indicates key pathological features of MS plaques. The increased Cho/Cr ratio found in Gd-enhancing plaques, in particular in the T(1) hypointense lesions, may reflect increased membrane cell turnover. The T(1) hypointense Gd unenhancing plaques better reflect axonal damage, as suggested by the decrease of NAA/Cr. Nevertheless, the lack of statistical differences in NAA/Cr between plaque subgroups suggests that axonal impairment might occur even in the early stages.

Adolescent↗
PubMed2000

An interrupted 34-CAG repeat SCA-2 allele in patients with sporadic spinocerebellar ataxia.

In spinocerebellar ataxia type 2 (SCA-2), a difference of three CAG repeats distinguishes normal alleles (14 to 31 repeats) from pathogenic alleles (34 to 57 repeats). All sequenced pathogenic alleles have a pure CAG repeat structure, whereas interrupted repeats have been seen exclusively in normal alleles. The authors present two patients with sporadic SCA with an interrupted 34-CAG repeat allele, (CAG)24(CAA)(CAG)9, who showed a phenotype compatible with SCA-2. The interrupted allele coding for a 34 pure polyglutamine tract may cause the SCA phenotype.

Aged↗
PubMed2000

Age at onset in multiple sclerosis.

Age at onset of multiple sclerosis (MS) can vary from childhood to adult life. Many reports have been carried out over the years concerning the role of age at onset in determining the disease outcome. In a sporadic MS population of 1463 patients with homogeneous clinical and demographic features, derived from three Italian neurological centres (Bari, Cagliari and Sassari), we analysed the relative weights of current age and age at onset on disease severity according to the expanded disability status scale (EDSS) score, by fixing the disease duration. The results of present study demonstrate that clinical disability in MS is influenced by the patient's age (p < 0.01) and not by the age at onset. Therefore, these data do not confirm the hypothesis that an early age at onset should be considered a favourable prognostic factor of the disease outcome.

Adolescent↗
PubMed2000

An attempt of identifying MS-associated loci as a follow-up of a genomic linkage study in the Italian population.

Subsequent to a genomic linkage study on Sardinian and Continental Italian families, we considered the possibility that some of the tested microsatellite markers showed association to MS. Markers selected on the basis of the data obtained in the original set of 70 multiplex families were tested for MS association in an additional set of 154 simplex families. A limited set of markers were further tested on an additional set of 100 simplex families. The results indicate the presence of a putative MS gene in 19q13.13.

Alleles↗
PubMed1999

Changes of serum sICAM-1 and MMP-9 induced by rIFNbeta-1b treatment in relapsing-remitting MS.

OBJECTIVE: To correlate changes in serum levels of intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases (MMP) with clinical and MRI evidence of disease activity in MS patients receiving treatment with interferon-beta (rIFNbeta)-1b. BACKGROUND: rIFNbeta reduces the frequency of gadolinium-enhancing (Gd+) MRI in relapsing-remitting MS (RRMS). Its mechanism of action on improving the integrity of the blood-brain barrier remains unclear. METHODS: sICAM-1 and MMP-9 and MMP-2 serum levels were longitudinally (24 months) investigated (ELISA; zymography) in correlation with the modifications of the integrated area under the curve of Expanded Disability Status Scale scores normalized to entry baseline (deltaEDSS AUC) and of GD+ MRI scans, and with neutralizing antibodies (NAB) to rIFNbeta-1b production (MxA) in 36 RRMS patients. RESULTS: During the first 12 months of treatment, levels of sICAM-1 increased and MMP-9 decreased significantly. After 12 months, levels returned toward baseline. Levels of sICAM-1 and MMP-9 were significantly negatively correlated. MMP-2 levels did not change significantly during the same period. During the second semester of the study, deltaEDSS AUC was significantly reduced. The percentage of patients with Gd+ MRI decreased significantly in the first (33%), second (29%), third (20%), and fourth (28%) semesters of treatment compared to baseline (62%). The NAB+ patients (14%) tended to have lower sICAM-1 levels at the ninth month; a higher MMP-9 activity at the sixth, 12th, and 18th months; and a greater deltaEDSS AUC in the third semester of treatment in comparison with the NAB- patients. CONCLUSIONS: These results show that rIFNbeta-1b therapy increases sICAM-1 serum levels and reduces serum MMP-9 activity.

Adjuvants, Immunologic↗
PubMed1999

Comparison of clinical and demographic features between affected pairs of Italian multiple sclerosis multiplex families; relation to tumour necrosis factor genomic polymorphisms.

We conducted a comparative analysis of clinical and demographic findings between pairs of relatives (36 sibling and 9 parent/child), concordant for Multiple Sclerosis (MS), from 40 MS Italian Multiplex families. A genetic TNF (alpha and beta) loci typing in 51 affected and 69 healthy relatives belonging to 25 of these families was also performed. The sib pairs resulted significantly concordant for age at onset (r=0.414, P<0.013), Progression Index (r=0.34, P<0.05) and sensory symptoms at onset (k=0.37), and significantly not concordant for sex (k=-0.37), whereas no concordance was found for year at onset and disease course. The only significant result in the small group of parent/child pairs was that parents developed MS at an age of 18.74 years significantly (P=0.020) greater than their children. Genomic analysis identified 13 variants of TNF-a alleles, 7 of TNF-b, 6 of TNF-d and 3 of TNF-e. No differences in the frequencies of the various TNF alleles were observed between affected and healthy relatives. The two-point lod-score analysis of the TNF locus showed not significant or negative results for the TNFalpha loci and slightly positive results (Zmax=0.4 at theta=0.2 cM) for the TNFbeta-b locus in the lowest penetrance dominant model. The Sib pair analysis, using combined TNFalpha and TNFbeta haplotypes, demonstrated a TNF allele sharing between affected sib-pairs which did not exceed the expected 50%. These results suggest that genetic factors may partially influence the disease onset and the progression rate in sibling pairs. A recall bias and/or an 'anticipation phenomenon' could explain the development of MS at an older age in parents than in their children. In this small-sized cohort of MS Italian families no significant associations were confirmed between TNF polymorphism and MS.

Adult↗
PubMed1999

Prenatal findings in trisomy 16q of paternal origin.

A 34-year-old pregnant woman was referred at 30 weeks of gestation with suspected fetal congenital heart disease. On prenatal ultrasound the following anomalies were detected: intra-uterine growth retardation, micrognathia, coarctation of the aorta with ventricular and atrial septal defects, ambiguous external genitalia, and clinodactyly of one hand with adducted thumb. Prenatal karyotyping was offered but refused by the patient. The fetus was delivered by Caesarean section due to fetal distress at 36 weeks of gestation. The neonate, weighing 2150 g was transferred to the neonatal intensive care unit, where he died 10 days later. The karyotype from peripheral blood lymphocytes was 46,XY+der(20)t(16;20)(q12.1;p13)pat. The maternal karyotype was unremarkable, whereas the father had the translocation t(16;20)(q12.1;p13). Necropsy confirmed all the prenatal findings. These are discussed together with the implications of the chromosomal diagnosis and the pertinent literature is reviewed.

Abnormalities, Multiple↗
PubMed1999

Linkage analysis of multiple sclerosis with candidate region markers in Sardinian and Continental Italian families.

Previous genome screens in multiple sclerosis have shown some evidence of linkage in scattered chromosomal regions. Although in no case the evidence of each single study was compelling and although in general the linkage 'peaks' of the different studies did not coincide, some regions can be considered likely candidates for the presence of MS risk genes because of the clustering of MLS scores and homology with eae loci. We performed a linkage analysis of markers in these regions and of intragenic markers of some individual candidate genes (HLA-DRB1, CTLA-4, IL9, APOE, BCL2, TNFR2). For the first time, Southern European populations were targeted, namely Continental Italians and Sardinians. A total of 69 multiplex families were typed for 67 markers by a semi-automatic fluorescence-based assay. Results were analysed for linkage by two non-parametric tests: GENEHUNTER and SimIBD. In general, the linkage scores obtained were low, confirming the conclusion that no gene is playing a major role in the disease. However, some markers, in 2p11, 3q21.1, 7p15.2 and 22q13.1 stood out as promising since they showed higher scores with one or the other test. This stimulates further association analysis of a large number of simplex families from the same populations.

Genetic Linkage↗