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Biomedical subjects

Enrico Granieri

Publications and source records attributed to Enrico Granieri.

At least 19 recordsLinked to original sources

Increased prevalence of varicella zoster virus DNA in cerebrospinal fluid from patients with multiple sclerosis.

In order to investigate the possible involvement of viruses in Multiple Sclerosis (MS), the study evaluated the presence of viral genomic sequences in cerebrospinal fluid (CSF), as markers of viral replication within the central nervous system (CNS). A total of 85 CSF samples were collected from 38 MS patients, 28 patients with other neurological diseases and 19 subjects without neurological diseases. Using nested-PCR, the investigation focused on the presence of human herpes virus DNA, including herpes simplex virus 1 (HSV-1) and 2 (HSV-2), the Epstein-Barr virus (EBV), varicella zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus 6 (HHV-6) and JC virus (JCV). All the CSF samples from the individuals without neurological diseases were negative for viral DNA. Genomic sequences of HSV-1, HCMV, EBV, HHV6, and JCV were found in patients with MS and other neurological diseases without significant differences between the two groups. VZV DNA was detected more frequently (P < 0.05) in the MS group (31.6%), particularly among the relapsing-remitting MS patients (43.5%), compared with patients with other neurological diseases (10.7%). In addition, the results indicated that JCV and HHV-6 were replicating actively in the CNS of a small, but significant number of patients with MS and other neurological diseases. Most importantly, the study revealed a high frequency of VZV DNA in the CSF of patients with MS, suggesting a possible role of this virus in the pathogenesis of MS.

Adult↗

The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNbeta exposure in multiple sclerosis.

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNbeta) in a large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44,140 patient-visits with a follow-up of 22,143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNbeta for up to 2 years, 39% for 2-4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR =0.23; 95% CI: 0.17-0.30) and worsening of relapse rate (HR =0.19; 95% CI: 0.14-0.27) were reduced by about 4-5-fold in patients exposed to IFNbeta for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNbeta treatment was lower (P <0.0001) in patients exposed to IFNbeta for up to two years than in other groups. A clinical stabilization over two years of IFNbeta exposure may predict a subsequent good clinical response to treatment.

Adjuvants, Immunologic↗

The excitability of the trigeminal motor system in sleep bruxism: a transcranial magnetic stimulation and brainstem reflex study.

AIMS: Since sleep bruxism (SB) is characterized by grinding and clenching of the teeth during sleep and could be an exaggerated manifestation of normal spontaneous rhythmic masticatory muscle activity, the aim of this study was to obtain a neurophysiological assessment of the excitability of the central jaw motor pathways in patients with signs and symptoms suggestive of SB. METHODS: A total of 30 subjects diagnosed with SB on the basis of self-report of tooth grinding were studied using the "recovery cycle" of the masseter inhibitory reflex (MIR) elicited by electric and magnetic stimulation of the mental nerves and by recording the motor potentials evoked in masseter muscles by transcranial magnetic stimulation. Tests were done during daytime, when the subjects were awake. The data obtained were compared with data from a population of normal subjects. RESULTS: In the putative SB patients and in normal subjects, the MIRs evoked by single electric and magnetic stimuli were similar. With paired stimuli, the degree of suppression of the late silent period was significantly lower (P < .01) in the patients compared to normal subjects, particularly for magnetic stimuli, at various interstimulus intervals. No significant differences were found between the 2 groups of subjects in the masseter motor potentials evoked by transcranial magnetic stimulation. CONCLUSION: Although the data were only obtained during wakefulness in patients self-reporting signs and symptoms suggestive of SB, the findings suggest that an abnormal excitability of the central jaw motor pathways may be present in SB subjects. This increased excitability could derive from an impaired modulation of brainstem inhibitory circuits and not from altered cortical mechanisms. These results support the view that bruxism is mainly centrally mediated and that it involves subcortical structures. The study also indicates that use of the MIR elicited by the double-shock technique could be valuable in the evaluation of bruxism.

Adult↗

Amyotrophic lateral sclerosis, rural environment and agricultural work in the Local Health District of Ferrara, Italy, in the years 1964-1998.

Previous epidemiological surveys, both analytic and descriptive, in the Local Health District (LHD) of Ferrara, northern Italy, have indicated that rural residence and agricultural work might constitute risk factors for Amyotrophic Lateral Sclerosis (ALS). The present investigation is a demographic survey in the LHD of Ferrara in the years 1964-1998 which aimed to verify whether the level of urbanization and agricultural activities might influence the risk of ALS. Based on the data obtained in a recent incidence study in the LHD of Ferrara which reported a mean annual crude incidence rate of ALS in the years 1964-1998 of 1.63 per 100,000 population (95 % CI 1.31-2.00), it was possible to compare the number of observed ALS cases and the number of expected ALS cases according to the level of urbanization and usual occupation on the basis of the residential and occupational pattern identified in the population of the LHD of Ferrara in the study period under the assumption of a homogeneous distribution of ALS. The present survey identified four different levels of urbanization in the LHD of Ferrara in the study period and for none of them was a difference between the number of observed and expected ALS cases found. Also in the most rural of the four identified levels of urbanization (small villages with an average population in the study period lower than 1,000 inhabitants and scattered houses in the countryside) no difference was found between observed and expected number of ALS cases (observed ALS cases 16, 95% Poisson CI 9.1-25.9, expected ALS cases 18.3). Based on the occupational pattern identified in the population of the LHD of Ferrara in the study period the number of incident cases of ALS whose usual occupation was in agricultural work exceeded the expected number (observed ALS cases 22, 95% Poisson CI 13.8-32.3, expected ALS cases 6.0). The present findings indicate that rural residence itself does not influence the risk of ALS while agricultural activities could influence the risk of ALS, with occupational exposure to agricultural chemicals playing a possible role.

Agriculture↗

Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated to a subset of multiple sclerosis patients with progressive forms.

The purpose of this study was to provide further insight into the effective relevance of the association between Chlamydia pneumoniae and MS. We evaluated by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae IgG in 46 relapsing-remitting (RR), 14 secondary progressive (SP) and 11 primary progressive (PP) MS patients grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Fifty-one patients with other inflammatory neurological disorders (OIND) and 52 with non-inflammatory neurological disorders (NIND) were used as controls. A C. pneumoniae-specific intrathecal IgG synthesis as detected by the relative specific index was present in a small proportion of MS (17%), OIND (22%) and NIND (2%) patients and was significantly more frequent in MS and in OIND than in NIND (p<0.001) and in SP and PP MS than in RR MS patients (p<0.02). Among the patients with C. pneumoniae-specific intratecally produced antibodies, CSF high-affinity anti-C. pneumoniae IgG were found in the majority of SP or PP MS, occasionally in OIND, but not in RR MS and NIND patients. These findings confirm that the presence of a humoral immune response to C. pneumoniae within the central nervous system (CNS) is not selectively restricted to MS, but is shared by several inflammatory neurological conditions. In addition, our results suggest that an intrathecal production of C. pneumoniae-specific high-affinity IgG can occur in a subset of patients with MS progressive forms in which a C. pneumoniae brain chronic persistent infection may play an important pathogenetic role.

Adult↗

Beneficial effect of interferon-beta 1b treatment in patients with relapsing-remitting multiple sclerosis is associated with an increase in serum levels of soluble HLA-I molecules during the first 3 months of therapy.

It has recently become clear that interferon-beta (IFN-beta) treatment is effective in ameliorating relapsing-remitting multiple sclerosis (RRMS) through an as yet unidentified mechanism. As there is no recognisable biological indicator to predict responsiveness to IFN-beta treatment, we have investigated fluctuations in serum sHLA-I levels in MS patients undergoing IFN-beta 1b therapy. Serum sHLA-I concentrations measured by enzyme-linked immunosorbent assay (ELISA) were assessed at baseline and, longitudinally, over a period of 18 months after the start of treatment in 29 RRMS patients grouped as responders and nonresponders according to their clinical response to IFN-beta 1b therapy. Thirty-nine healthy volunteers served as controls. Serum sHLA-I concentrations were significantly higher (p<0.001) in pretreated RRMS patients than in healthy donors. In MS patients, changes in mean serum levels of sHLA-I from baseline showed a temporal pattern characterized by a strong increase in the first trimester of treatment, a return toward basal values in the following 6 months, a slight decline at 12th and 15th months and a further moderate increase at the 18th month. Mean serum sHLA-I levels were significantly more elevated in responders than in nonresponders at the first (p<0.02), second (p<0.01), and at third (p<0.02) months after the beginning of treatment and significantly lower (p<0.01) at the time of relapses in comparison to baseline values. Overall, these results seem to indicate that IFN-beta 1b can modulate fluctuations in serum sHLA-I levels and argue in favour of a potential role for serum levels of sHLA-I as a sensitive marker to monitor response to IFN-beta treatment in MS.

Adult↗

Pregnancy as a risk factor for restless legs syndrome.

Pregnant women have at least two or three times higher risk of experiencing restless legs syndrome (RLS) than the general population. These data come from few epidemiological studies finding an 11-27% prevalence of RLS during pregnancy. Women affected by pre-existing RLS often complain of worsening symptoms during pregnancy. This is usually a benign form of RLS, with the highest degree of severity in the third trimester and a tendency to disappear around delivery. The causes of the association between RLS and pregnancy are unknown. The most debated hypotheses are: metabolic alterations, with particular regard to iron and folate deficiency; hormonal influences related to the increase of prolactin, progesterone and estrogens during late pregnancy; and the changing motor habits and psychological state of pregnant women. The importance of folate and iron supplementation during pregnancy in preventing RLS is unclear. RLS in pregnant women is frequently unrecognized; they are often worried about the symptoms and do not receive an adequate explanation by doctors.

Anemia, Iron-Deficiency↗

Is there a decrease in Guillain-Barré syndrome incidence after bovine ganglioside withdrawal in Italy? A population-based study in the Local Health District of Ferrara, Italy.

There have been many reports of cases of Guillain-Barré syndrome (GBS) after therapeutic injection of bovine ganglioside preparations with the result that they were withdrawn in Italy in December 1993. As the relationship between bovine gangliosides and GBS has not yet been established, a further epidemiological investigation in the Local Health District (LHD) of Ferrara, Italy, was carried out in the years 1994-2001 to verify whether the incidence of GBS had changed after ganglioside withdrawal. The other aim of this investigation was to update the incidence of GBS in this area since the two previous investigations we carried out showed an increase in incidence from the years 1981-1987 to the years 1988-1993. The cases of GBS were identified prospectively. To guarantee completeness of case ascertainment, an intensive retrospective survey of all possible sources of cases for the entire study period was performed. The mean annual crude incidence rate in the years 1994-2001 (based on 26 new cases) was 1.97 per 100,000 population (95% CI 1.29-2.89), whereas it had been 1.87 per 100,000 population (95% CI 1.35-2.52) in the years 1981-1993 (based on 43 cases) when gangliosides were available. The age-adjusted rates were almost identical (1.66 and 1.65 per 100,000 population, respectively). Although ganglioside administration could have triggered, on the basis of an individual susceptibility, an immunologic reaction which produced GBS, the incidence of GBS in the study area did not change after ganglioside withdrawal. In the whole period 1981-2001, a temporal pattern of incidence was reported with an increase towards a peak in 1990-1992 and a progressive decline thereafter. This temporal pattern did not seem related to ganglioside withdrawal, and no definite explanation for it was found which could imply that the disease incidence is less stable than it was deemed.

Adolescent↗

Molecular identification and antibody testing of Chlamydophila pneumoniae in a subgroup of patients with HIV-associated dementia complex. Preliminary results.

Chlamydophila pneumoniae DNA was investigated by polymerase chain reaction (PCR), in cerebrospinal fluid (CSF) specimens from patients suffering from HIV-1-associated dementia complex (HADC). Four (17.3%) cases of C. pneumoniae infection were identified among 23 HADC individuals with DNA amplification of major outer membrane protein (MOMP) gene and 16S rRNA gene sequences. Sequence analysis revealed significant homologies with C. pneumoniae compared to Chlamydia trachomatis and Chlamydia psittaci. High mean levels of CSF specific anti-C. pneumoniae antibodies and C. pneumoniae antibody specific index values significantly elevated were also found by enzyme-linked immunosorbent assay (ELISA) in these patients. The results suggest a hypothetical role of C. pneumoniae in the pathogenesis or progression of HADC.

AIDS Dementia Complex↗

Presence of detectable levels of soluble HLA-G molecules in CSF of relapsing-remitting multiple sclerosis: relationship with CSF soluble HLA-I and IL-10 concentrations and MRI findings.

We have investigated the presence of non-classical soluble HLA-G molecules (sHLA-G) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients and the possible relationships between CSF levels of sHLA-G, classical soluble HLA-I (sHLA-I) molecules, IL-10 amounts and Magnetic Resonance Imaging (MRI) findings were evaluated. We studied by ELISA technique the sHLA-I, sHLA-G and IL-10 levels in CSF of 50 relapsing-remitting (RR) MS patients stratified according to clinical and MRI evidence of disease activity. Thirty-six patients with other inflammatory neurological disorders (OIND) and 41 with non-inflammatory neurological disorders (NIND) were used as controls. CSF mean levels were significantly higher in MS and OIND than in NIND for sHLA-I (p<0.001) and in MS than in controls for sHLA-G (p<0.001), with no differences among the various groups for IL-10 mean concentrations. An increase in CSF sHLA-I was found in MS patients with Gd-enhancing lesions (p<0.01), while sHLA-G and IL-10 were more represented in MS patients without lesional activity on MRI scans (p<0.02). In MRI-inactive MS, CSF IL-10 mean concentrations were significantly greater in patients with CSF-detectable levels of sHLA-G than in those without any evidence of CSF sHLA-G expression (p<0.05). Our findings suggest that CSF classical sHLA-I and non-classical sHLA-G levels may modulate MS activity as assessed by MRI acting in opposite directions. The association observed between sHLA-G and IL-10 when Gd-enhancing lesion resolved indicates a potential immunoregulatory role for IL-10 in the control of MS disease activity by shifting the sHLA-I/sHLA-G balance towards sHLA-G response.

Adult↗

Patient demographic and clinical features and circadian variation in onset of ischemic stroke.

BACKGROUND: Studies have reported circadian variation in the onset of ischemic stroke, which may carry important pathophysiological implications. However, there is no detailed information about circadian variations among the subtypes of stroke. OBJECTIVE: To determine whether subgroups of patients with ischemic stroke with specific clinical characteristics would exhibit different circadian patterns, to more systematically examine the role of possible triggering or precipitating factors. DESIGN AND SETTING: Analysis of the effects of demographic, medical, and pathophysiological factors on the circadian pattern of an unselected series of patients with ischemic stroke consecutively admitted to our hospital. RESULTS: The study included 1656 patients. As in other studies, the peak of stroke onset occurred in the morning, with a second peak in the evening. Circadian variation in ischemic stroke onset was shown to be independent of clinical variables considered. CONCLUSIONS: Our study confirms the circadian rhythm of stroke reported in previous studies. There is a chronological pattern of ischemic stroke in the morning, which appears to be independent of the presence of risk factors and of clinical stroke subtypes. The role of circadian variability of blood pressure (present in patients with and without hypertension) and a concurrent morning hypercoagulability are suggested as possible determinants of this pattern. Preventive pharmacological interventions aimed at specifically targeting the morning rise in risk factors could be advantageous in reducing the overall risk of ischemic stroke.

Aged↗

Clinical and MRI disease activity in multiple sclerosis are associated with reciprocal fluctuations in serum and cerebrospinal fluid levels of soluble HLA class I molecules.

The goal of our study was to clarify the contribution of soluble human leukocyte antigens class I (sHLA-I) in multiple sclerosis (MS) immune dysregulation. We retrospectively evaluated by ELISA cerebrospinal fluid (CSF) and serum sHLA-I levels in 79 relapsing-remitting (RR), 26 secondary progressive (SP) and 15 primary progressive (PP) MS patients stratified according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. One hundred and nine patients with other inflammatory neurological disorders (OIND), 88 with noninflammatory neurological disorders (NIND) and 82 healthy donors were used as controls. An intrathecal synthesis of sHLA-I detected by a specific index was significantly more consistent in MS than in controls, with more pronounced values in MS patients with relapses and MRI enhancing brain lesions. A decrease in serum sHLA-I concentrations was observed in MS patients with demyelinating attacks, while an increase in CSF levels of sHLA-I was found in MS patients with lesional activity on MRI scans. This association between intrathecal synthesis and reciprocal fluctuations of CSF and serum levels of sHLA-I in clinically and MRI active MS seems to suggest a potential role for CSF and serum levels of sHLA-I as a sensitive marker of immune activation taking place both intrathecally and systemically in MS.

Adult↗

Risk factors for cryptogenic and idiopathic partial epilepsy: a community-based case-control study in Copparo, Italy.

OBJECTIVES: The etiology of epilepsy remains unknown in most cases. We sought to investigate the role of some pre-, peri- and postnatal factors in the etiology of idiopathic and cryptogenetic partial epilepsy. METHODS: We carried out a community-based case-control study using the incidence cohort of epileptic patients living in the district of Copparo, in the province of Ferrara, Italy. The study was performed in 55 cases and 165 controls. A standardized questionnaire was used to collect information in face-to-face interviews. RESULTS: Multivariate logistic regression analysis found that a personal history of febrile convulsions [odds ratio (OR) = 4.01, 95% confidence interval (CI) = 1.3-19.1] and a family history of seizures in first-degree relatives (OR = 4.5, 95% CI = 1.8-18.6) were independent risk factors for the condition under study. We failed to demonstrate an association between partial epilepsy and previously suggested perinatal risk factors. CONCLUSION: The findings of this study further support the hypothesis of a genetic propensity for seizures, which may be expressed early by the occurrence of febrile convulsions.

Adolescent↗