Biomedical subjects

P Livrea

Publications and source records attributed to P Livrea.

At least 19 recordsLinked to original sources

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

Primary cervical dystonia and scoliosis: a multicenter case-control study.

OBJECTIVE: To study the distribution of prior scoliosis among patients with primary adult-onset cervical dystonia (CD) and matched control subjects. METHODS: Case and control subjects were selected among consecutive outpatients attending four Italian centers. Control outpatients were matched for age (+/-5 years), sex, and referral center. Information on prior scoliosis, other spine diseases, and family history of dystonia was obtained by a standardized questionnaire and supported by medical records. Conditional logistic regression models were used to adjust simultaneously for age, disease duration, and education level and to determine the independent association of exposure variables with the outcome. RESULTS: Prior scoliosis developing in middle or late childhood or at around the puberty occurred more frequently among 72 case patients than among 144 neurologic control subjects. No subject reported conditions considered to be responsible for secondary scoliosis. The association of scoliosis and CD was not confounded by age, duration of disease, education level, other spine diseases, or family history of dystonia (adjusted odds ratio [OR] 6.8; 95% CI 1.5 to 29.5; p = 0.011). The OR of family history of dystonia (18.7; 95% CI 2.4 to 147.5; p = 0.005) fell to 11.7 (95% CI 1.3 to 103; p = 0.03) after controlling for scoliosis. CONCLUSIONS: Prior scoliosis may increase the risk of developing CD. The observed decrease in the magnitude of the association between family history of dystonia and CD after controlling for scoliosis suggests a link between the two conditions.

Adolescent↗

PubMed2003

Does sex influence age at onset in cranial-cervical and upper limb dystonia?

The relation between age at dystonia onset and sex was investigated in 264 patients with cranial-cervical dystonia and 56 patients with upper limb dystonia. In cranial-cervical dystonia, women had a significantly greater age at the onset of dystonia than men. The association was independent of duration of disease and distance of referral, but it was no longer detectable after adjustment for educational level. In upper limb dystonia, men and women did not differ for age at dystonia onset, duration of disease, education level, or distance of referral. A significant inverse association between age at the onset of dystonia and education was observed in both cranial-cervical dystonia and upper limb dystonia series.

Adult↗

PubMed2003

Agreement among neurologists on the clinical diagnosis of dystonia at different body sites.

OBJECTIVE: To study the reliability of the diagnosis of blepharospasm, oromandibular dystonia, cervical dystonia, and writer's cramp among neurologists. METHODS: 12 patients with adult onset focal segmental dystonia were videotaped in a standardised way. The tape was sent to six neurologists who are involved in clinical practice without a specific interest in movement disorders (general neurologists), and to four neurologists expert in movement disorders. The observers had to recognise whether the patients were affected by dystonia and to distinguish among blepharospasm, oromandibular dystonia, cervical dystonia, and writer's cramp. Interobserver reliability was assessed by kappa statistics, and the degree of agreement was classified according to the Landis classification. RESULTS: The 10 neurologists reached slight to moderate agreement on the diagnosis of these four disorders. When the observers were subdivided according with their professional experience in the field, a moderate to perfect agreement on the diagnosis was achieved by specialists in movement disorders, and a fair to moderate agreement by the general neurologists. CONCLUSIONS: Neurologists may have different ability to recognise adult onset focal dystonia, depending on their experience and on the type of dystonia.

Adult↗

PubMed2003

Influence of age on the association between primary hemifacial spasm and arterial hypertension.

OBJECTIVE: To investigate the association between primary hemifacial spasm and arterial hypertension. SUBJECTS: 114 patients with primary hemifacial spasm and 228 neurological controls, matched for age, sex, and referral centre, were recruited during an 18 month period from consecutive outpatients attending two neurological institutions. DESIGN: The association between exposure variables and case/control status was examined in conditional logistic regression models, adjusting simultaneously for disease duration and education level. RESULTS: Hypertension was more common among the patients with primary hemifacial spasm than among the controls. The association was independent of age, disease duration, years of schooling, and other diseases (adjusted odds ratio (OR) 2.76 (95% confidence interval (CI), 1.43 to 5.33); p = 0.002). Hypertension was associated with hemifacial spasm in both the left sided group (adjusted OR, 2.76 (1.18 to 6.44); p = 0.02) and the right sided group (adjusted OR, 3.02 (1.13 to 8.1); p = 0.03). The association of hypertension with hemifacial spasm was apparently greater in the age group < 60 years (adjusted OR, 4.2 (1.4 to 12); p = 0.008) than in the age group >/= 60 years (adjusted OR, 2.5 (CI 1.3 to 4.6); p = 0.005), but the difference in the OR estimates between the two age groups was not significant. Among hypertensive patients, mean age at the diagnosis of hypertension was significantly lower than mean age at the onset of hemifacial spasm in the age group >/= 60 years, but not significantly different in the age group < 60 years. CONCLUSIONS: The findings support the hypothesised association of primary hemifacial spasm with hypertension and raise the possibility that a different mechanism underlies the association in different age groups.

Adolescent↗

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

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

Prevalence of primary blepharospasm in a community of Puglia region, Southern Italy.

The authors ascertained the prevalence of primary blepharospasm (BSP) in a community located in Puglia, a region in Southern Italy, by focusing on neurologists and ophthalmologists. The crude prevalence rates were 133 per million (95% CI, 61--153) for both focal and segmental BSP, 74 per million (95% CI, 24--173) for focal BSP, and 59 per million (95% CI, 16--151) for segmental BSP. Prevalence rate increased with age. Apraxia of eyelid opening and BSP coexisted in one third of cases.

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

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↗

PubMed2001

Proton MR spectroscopy in idiopathic spasmodic torticollis.

Single-voxel proton magnetic resonance spectroscopy (1H-MRS), localised to the basal ganglia, was used to determine changes in metabolite levels in idiopathic spasmodic torticollis (IST). We examined nine patients and 13 healthy subjects. The mean values (+/- SD) of peak area ratios were: IST: N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) 1.79 +/- 0.39, NAA/creatine and phosphocreatine compounds (Cr) 1.61 +/- 0.38, Cho/Cr 0.91 +/- 0.19; controls: NAA/Cho 2.07 +/- 0.35, NAA/ Cr 1.82 +/- 0.31, Cho/Cr 0.89 +/- 0.12. Statistical analysis showed that NAA/Cho and NAA/Cr were significantly lower in patients than in controls (P = 0.0304 and 0.0431, respectively). These results indicate a reduction in NAA, and suggest striatal involvement in the pathogenesis IST.

Adolescent↗

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↗

PubMed2000

Interferon beta-1a downregulates TNFalpha-induced intercellular adhesion molecule 1 expression on brain microvascular endothelial cells through a tyrosine kinase-dependent pathway.

TNFalpha (100 U/ml, 24 h) upregulated intercellular adhesion molecule 1 (ICAM1) expression on brain microvascular endothelial cell (BMEC) culture. The tyrosine kinase (TK) inhibitor genestein (100 microgram/ml), the protein kinase C (PKC) inhibitor staurosporin (1 nM), and interferon (IF) beta-1a (1000 U/ml) antagonized TNFalpha effect. When an ineffective dose of IFbeta-1a (100 U/ml) was challenged with ineffective doses of either genestein (10 microgram/ml) or staurosporin (0.1 nM), the combination IFbeta-1a-genestein significantly reduced TNFalpha-induced ICAM1 expression whereas IFbeta-1a-staurosporin did not. These findings indicate that a TK- rather than a PKC-dependent mechanism is involved in the modulation of TNFalpha response by IFbeta-1a on BMECs.

Adjuvants, Immunologic↗

PubMed2000

Inhibition of protein kinase C counteracts TNFalpha-induced intercellular adhesion molecule 1 expression and fluid phase endocytosis on brain microvascular endothelial cells.

TNFalpha (100 U/ml, 24 h) upregulated intercellular adhesion molecule 1 (ICAM1) expression and fluid phase endocytosis (FPE) of horseradish peroxidase on brain microvascular endothelial cell (BMEC) culture. The protein kinase C (PKC) inhibitor staurosporin (0. 5-10 nM) antagonized ICAM1 expression and FPE due to TNFalpha, whereas the protein kinase A inhibitor H89 (0.5-10 nM) did not. These findings indicate that a PKC-dependent mechanism may affect TNFalpha signalling on different barrier properties of BMECs.

Animals↗

PubMed2000

Primary hemifacial spasm and arterial hypertension: a multicenter case-control study.

In a case-control study, the authors found that arterial hypertension occurred more frequently among 115 patients with primary hemifacial spasm than among 115 neurologic controls matched for age (+/-5 years), sex, and referral center. The association was not confounded by education level, smoking history, diabetes, or other diseases (adjusted OR 2.64; 95% CI 1.3 to 5.33, p = 0.007). Hypertension was significantly associated with the outcome in the left-sided group (OR 4.0; 95% CI 1.4 to 11.5), but data concerning patients with right-sided spasm were inconclusive (OR 1.05; 95% CI 0.36 to 3.1). In our sample, hypertension either preceded or followed the onset of hemifacial spasm.

Aged↗

PubMed2000

Interferon beta-1a prevents the effects of lipopolysaccharide on embryonic brain microvessels.

By means of light and electron microscopy we have studied the effect of interferon beta-1a (IFNbeta-1a) in the optic tecta of 20-day-old chick embryos under normal conditions and after exposure to lipopolysaccharide (LPS) which mimics the blood-brain barrier (BBB) disruption in meningoencephalitis. Optic tecta were examined for: (i) ultrastructure by means of transmission electron microscopy; (ii) the immunohistochemical localization of HT7 antigen, a specific marker of differentiation of the brain microvessels; (iii) the brain microvessel permeability, by means of horseradish peroxidase (HRP) tracer; (iv) the expression of microvessel glycoconjugates, by means of lectin histochemistry, using Ricinus communis agglutinin-I (RCA-I), specific for beta-D-galactosyl moieties and Wheat Germ agglutinin (WGA) specific for sialyl and N-acetylglucosaminyl moieties. A morphometric evaluation of brain microvessel permeability and of glycoconjugate expression was also performed. In control- and in IFNbeta-1a-treated embryos, HRP was confined to the vessel lumina which were sealed by the interendothelial tight junctions. RCA-I binding sites were recognizable both in the basal membranes and in the tight junctions, while WGA sites were present on the luminal side of the endothelial cells. HRP was blocked in the vessels lumina by the interendothelial tight junctions. After LPS treatment, HRP showed an extravascular localization and the labeling of microvessels by anti-HT7 antibodies disappeared. RCA-I binding was only found ultrastructurally and appeared as irregularly clustered gold particles, in the cleft of damaged tight junctions, but were no longer detectable in the endothelial basement membranes. After pretreatment of LPS-treated embryos with IFNbeta-1a, the vessel permeability to HRP strongly decreased and the vessels showed the normal pattern of HT7 protein and of the RCA-I binding sites. These results indicate that the changes induced by LPS in the endothelial cells are prevented by IFNbeta-1a.

Animals↗

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

Early onset multiple sclerosis.

Multiple sclerosis (MS) onset is usually in adult life (age 20-40 years). Discordant data have been reported concerning the frequency of early onset MS (EOMS) that ranges from 2.7% to 5%, whereas there is a general agreement on prevalence of female sex, particularly after puberty. The initial symptoms in EOMS are frequently characterized by visual loss whereas the other functional systems are involved with a variable frequency. Literature data show that EOMS tends to have a relapsing-remitting course, a high rate of recovery from the initial attack, a long time interval between the first and second attacks and a slow progression rate. A poor prognosis is reported in a few cases of EOMS and seems to be related to number of relapses and to the delay between the first and second attacks.

Adolescent↗