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Biomedical subjects

A Ghezzi

Publications and source records attributed to A Ghezzi.

At least 19 recordsLinked to original sources
PubMed2006

Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphisms influence cardiovascular events rate during statin treatment.

BACKGROUND: Oxidized-LDL (ox-LDL) are involved in atherothrombosis by induction of endothelial dysfunction and thrombosis. The specific receptor lectin-like oxidized-LDL receptor-1 (LOX-1) is expressed in endothelial cells, monocytes and platelets. LOX-1 gene allelic variants (3'UTR/T) have been related with cardiovascular events and reduced anti-platelet activity induced by statins. OBJECTIVES: To detect whether LOX-1 polymorphisms could affect statins effectiveness in cardiovascular prevention. PATIENTS/METHODS: The present was a retrospective study performed in 751 white hypercholesterolemic subjects treated with increasing doses of atorvastatin (n=382, 247 male, 135 female) or simvastatin (n=369, 244 male, 125 female) up to 4 years, whose LDL target was 3.36 mmol/L according to the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATPIII). Single nucleotide polymorphism were evaluated by allelic discrimination assays (PCR), lipid profile by enzymatic-colorimetric methods and C-reactive protein (CRP) by a nephelometric technique. RESULTS: Twenty-three non-ST elevation (NSTEMI) and eleven ST-elevation myocardial infarction (STEMI) were encountered in the observational period without differences between treatments (p=0.175) and sex (p=0.139). Each symptomatic subject (10 reaching the appropriate LDL target and 24 with still undesirable LDL) had the 3'UTR/T allelic variant (adjusted O.R. 4.63, 95% C.I. 3.46-6.70, p<0.0001). Among patients not reaching LDL target the C allele resulted protective with respect to T carriers (p<0.00001). Also, similar changes of CRP resulted in different event rate between T and C carriers (p<0.001) in the whole cohort. CONCLUSIONS: In the studied population LOX-1 genetic variants influence cardiovascular risk reduction induced by statins also in patients not reaching the LDL target. The previously described LOX-1-related antithrombotic actions of both statins employed could have a specific role in what observed, suggesting a genetic influence in statins LDL-lowering partially related actions.

Aged↗
PubMed2006

Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years.

Reliable prognostic markers of primary progressive (PP) multiple sclerosis evolution are still needed. Diffusion tensor (DT) MRI can quantify normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis patients. We investigated whether conventional and DT-MRI-derived measures can predict the long-term clinical evolution of PP multiple sclerosis. In 54 PP multiple sclerosis patients, conventional and DT-MRI scans of the brain and T1-weighted scans of the cervical cord were acquired at baseline and after a median follow-up of 15 months. Another clinical evaluation was performed, 56 months after baseline, in 52 patients. Measures of lesion load, brain and cord atrophy were obtained. Histograms of the mean diffusivity (MD) and fractional anisotropy (FA) values from the NAWM and GM were analysed. At follow-up, 35 patients (65%) experienced a confirmed disability progression. Baseline expanded disability status scale score and average GM MD were independent predictors of subsequent clinical deterioration in a multivariable model (Nagelkerke R2: 0.44; discriminating ability: 81%). A lower level of disability and a more severe GM damage identify PP multiple sclerosis patients with an increased risk of disease progression over the subsequent 5 years. These data may be relevant to select patients for future exploratory phase II trials.

Adult↗
PubMed2006

Grading cervical cord damage in neuromyelitis optica and MS by diffusion tensor MRI.

The authors assessed the ability of diffusion tensor MRI to grade cervical cord damage in 10 patients with neuromyelitis optica, 10 patients with multiple sclerosis, and 10 healthy controls. The three groups differed in terms of average mean diffusivity (p = 0.008) and average fractional anisotropy (p = 0.04). There was a correlation between the Expanded Standard Disability Status Scale score and cord average mean diffusivity (r = 0.52, p = 0.02).

Adult↗
PubMed2006

MRI quantification of gray and white matter damage in patients with early-onset multiple sclerosis.

BACKGROUND AND OBJECTIVE: Contrary to what happens in adult-onset multiple sclerosis (MS), in a previous preliminary magnetic resonance imaging (MRI) study we showed only subtle normal-appearing brain tissue changes in patients with earlyonset MS. Our objective was to evaluate the presence and extent of tissue damage in the brain normalappearing white matter (NAWM) and gray matter (GM) from a larger population of patients with earlyonset MS. METHODS: Using diffusion tensor (DT) and magnetization transfer (MT) MRI, we obtained DT and MT ratio (MTR) maps of the NAWM and GM from 23 patients with early-onset MS and 16 sex- and age-matched healthy volunteers. RESULTS: Compared with healthy volunteers, patients with early-onset MS had significantly increased average MD (p = 0.02) and FA peak height (p = 0.007) and decreased average FA (p <0.0001) of the NAWM. Brain dual-echo lesion load was significantly correlated with average FA (r = -0.48, p = 0.02) and with FA peak height (r = 0.45, p = 0.03) of the NAWM. No MTR and diffusion changes were detected in the GM. CONCLUSIONS: This study confirms the paucity of the 'occult' brain tissue damage in patients with earlyonset MS. It also suggests that in these patients GM is spared by the disease process and that NAWM changes are likely to be secondary to Wallerian degeneration of fibers passing through macroscopic lesions.

Adolescent↗
PubMed2006

Intensive immunosuppression in multiple sclerosis.

Immunosuppressive drugs have been used out of label in multiple sclerosis (MS) for over 30 years and around 10% of patients are actually under immunosuppressive treatment. The rationale for immunosuppression in MS lies in the hypothesis that MS is an inflammatory immune-mediated disease that can take advantage of strong anti-inflammatory activity. Azathioprine, methotrexate, cyclophosphamide and mitoxantrone are the most utilised agents, but only the latter has been approved for clinically active MS. Many of them are safe in combination with interferon-beta and are under investigation in controlled trials. Plasma exchange is limited to catastrophic attacks in refractory MS whilst bone marrow transplantation is considered in patients with an extremely severe, active disease as the final option in escalation therapy. Although immunosuppressants are best effective in induction therapy, their use is limited by toxicity and potential long-term risk.

Combined Modality Therapy↗
PubMed2005

Axonal injury in early multiple sclerosis is irreversible and independent of the short-term disease evolution.

OBJECTIVE: To define the nature and the temporal evolution of neuronal/axonal injury in patients at the earliest clinical stage of multiple sclerosis (MS), using whole brain N-acetylaspartate (WBNAA) proton MR spectroscopy (1H-MRS). METHODS: Thirty-five patients at presentation with clinically isolated syndromes (CIS) and MRI evidence of disease dissemination in space were studied. The following scans of the brain were acquired within 3 months from the onset of the disease and after 12 months: 1) dual-echo; 2) WBNAA 1H-MRS; 3) pre- and postcontrast T1-weighted. The same scans were obtained in 12 age-matched healthy subjects, without contrast administration. In patients, conventional MRI scans were also repeated 3 months after the first scanning session, to assess the presence of early disease dissemination in time (DIT). RESULTS: Over the study period, 24 patients showed MRI evidence of disease DIT, thus fulfilling the criteria for a diagnosis of MS. The average WBNAA amount was lower in CIS patients than in controls both at baseline (13.7 vs 16.9 mM, p < 0.001) and at 1-year follow-up (12.6 vs 16.2 mM, p < 0.001), but the average yearly percentage change of WBNAA did not differ between the two groups. No MRI or 1H-MRS quantities were significantly associated with the disease DIT over the study period. CONCLUSION: Irreversible brain damage associated with axonal dysfunction occurs at a very early stage in patients with clinically isolated syndromes, but it does not seem to be related with the disease evolution in the subsequent short-term period.

Adult↗
PubMed2005

Immunomodulatory treatment of early onset multiple sclerosis: results of an Italian Co-operative Study.

The ITEM study group was organised in Italy to evaluate the effectiveness and safety of interferon-beta (IFNbeta) and glatiramer acetate (GA) in multiple sclerosis (MS) patients treated before 16 years of age. Eighty-six patients (58 females) were included in our database: as subjects with pre- and treatment duration <3 months were excluded, the data of 81 subjects were analysed: 51 were treated with IFNbeta-1a 6 million once weekly (Avonex), 19 with IFNbeta three times weekly (16 with Rebif, 3 with Betaferon) and 11 with GA (Copaxone). The mean age at onset was 12.4 (SD 2.4) years and the mean pre-treatment duration was 19.7 (SD 25.5) months. After a treatment duration of 36.1 (SD 24.2) months, the mean annualised relapse rate decreased from 2.8 (SD 2.6) to 0.5 (SD 0.7). The EDSS score remained unchanged (basal=1.4, final=1,4). Clinical side effects were recorded in 46 subjects of the IFNB group, transient in 35 (flu-like syndrome in 24, headache in 12, myalgia in 10, injection reaction in 5, fever in 3) and persistent in 11 (headache in 5, fever in 4, flu-like syndrome in 3, myalgia in 3, injection reaction in 1). In the GA-treated group, side effects were recorded in 3 cases: injection reaction in 2 and transient chest pain in 1. Abnormal laboratory findings (mainly reduction of WBC) were observed in 24 subjects (transient in 22). Nine subjects treated with Avonex discontinued the treatment: 7 shifted to Rebif, 2 stopped the therapy. Four subjects treated with INFbeta three times weekly shifted to other medications and 2 increased the dose. Four subjects treated with GA discontinued the treatment: 3 shifted to other medications and 1 stopped GA because of injection reaction. On the whole, 3 cases stopped the treatment definitively. To conclude 81, clinically definite MS subjects were treated during childhood or adolescence with immunomodulatory drugs. The treatment was generally well tolerated. It reduced the relapse rate and the progression of the disease in most cases.

Adjuvants, Immunologic↗
PubMed2005

Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study.

OBJECTIVE: Immunomodulatory drugs (IDs) (interferon beta (IFNgamma) and glatiramer acetate (GA)) reduce relapse rate and disease progression in relapsing remitting multiple sclerosis (RRMS) but extensive data are not available on the effectiveness and tolerability of these drugs in childhood or adolescence. The aim of this study was to evaluate the impact of IFNbeta and GA in MS patients treated before 16 years of age. METHODS: A research group (Immunomodulatory Treatment of Early onset MS (ITEMS)) was promoted in Italy to collect a large series of patients affected by clinically definite and RRMS and treated with IDs before 16 years of age. Fifteen centres recognized subjects suitable for inclusion: 76 patients (52 females) were collected with a mean age at onset of 12.4 (SD 2.5) years, a mean disease duration of 18.6 (SD 14.7) and a relapse rate of 3.1 (SD 2.9). RESULTS: Results were evaluated in 65 (45 females) subjects with a pretreatment and a treatment duration >3 months: 38 were treated with IFNbeta-1a once weekly (Avonex), 18 with IFNbeta three times weekly (16 with Rebif, 2 with Betaferon) and nine with GA (Copaxone). The mean pretreatment period was respectively 20, 18 and 9.2 months. The treatment duration lasted respectively 23.3, 40.7 and 33.3 months. The mean annualized relapse rate decreased dramatically during the treatment: from 2.4 to 0.4 in the Avonex group, from 3.2 to 0.8 in the Rebif-Betaferon group and from 2.8 to 0.25 in the GA group. The mean final EDSS scores were respectively (in brackets the initial scores): 1.3 (1.4), 1.6 (1.8) and 0.6 (1.1). In the whole group, the final score was unchanged or reduced in all subjects except eight. Clinical side effects were recorded in 41/65 subjects (mainly in subjects treated with IFNbeta), abnormal laboratory findings were observed in 13/65 subjects: they were transient in most cases. IFNgamma was stopped in six cases: in four because of inefficacy and in two cases because of side effects. CONCLUSIONS: Sixty-five clinically definite MS subjects were treated during childhood or adolescence with IDs. The treatment reduced the relapse rate and the progression of the disease in most cases. Side effects were common in subjects treated with IFNbeta but were well tolerated in most cases.

Adjuvants, Immunologic↗
PubMed2004

The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study.

In a multicenter cross-sectional study, the authors assessed pain in patients with multiple sclerosis (MS) using a symptom-oriented approach. Out of 2,077 questionnaires, we used 1,672 for data analysis. Pain and frequencies included trigeminal neuralgia 2%, Lhermitte's sign 9%, dysesthetic pain 18.1%, back pain 16.4%, and painful tonic spasms 11%. Comparison between different groups showed significant differences for age, Expanded Disability Status Scale, disease duration, and disease course, but not for sex. This study underlines the relevance of pain in the clinical history of MS.

Adolescent↗
PubMed2004

An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS.

Cervical cord magnetization transfer ratio (MTR) histograms were obtained from 45 patients at presentation with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). The mean values of MTR histogram-derived metrics were not different between CIS patients and healthy control subjects or between patients with and without evidence of disease dissemination in time. Only three patients showed significantly lower cord MTR values than control subjects. These findings suggest the absence of intrinsic structural damage of the cervical cord soon after the onset of CIS suggestive of MS, even in those patients with an early evolution to MS.

Adolescent↗
PubMed2004

Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica.

Using magnetization transfer (MT) and diffusion tensor (DT) MRI, the authors assessed the extent of tissue damage of the brain normal-appearing white and gray matter (NAGM) in patients with neuromyelitis optica (NMO). Compared to healthy controls, patients with NMO showed reduced MT ratio and increased mean diffusivity of the NAGM. This challenges the classic notion of a sparing of the brain tissue in the course of NMO.

Adult↗
PubMed2004

Italian version of the Chicago multiscale depression inventory: translation, adaptation and testing in people with multiple sclerosis.

Depression is the commonest psychiatric disturbance in people with multiple sclerosis (MS), with prevalence higher than in the general population and other chronic diseases. However, accurate assessment of depressive symptoms can be biased by somatic symptoms which are part of both MS and depression. We translated and adapted into Italian the Chicago multiscale depression inventory (CMDI) and assessed its acceptability, internal consistency and test-retest reliability in 213 MS outpatients and 213 individually matched healthy controls. The questionnaire was also tested in 32 people with major depression. Acceptability, internal consistency, and test-retest reliability were good overall. We found greater odds for depressive symptoms in people with MS than healthy controls, with highest odds ratio for somatic symptoms (vegetative subscale). The Italian CMDI is characterized by good acceptability, internal consistency, and test-retest reliability. These findings support the use of the CMDI in Italian subjects with MS to screen for and follow depressive symptoms.

Adolescent↗
PubMed2004

Clinical characteristics of multiple sclerosis with early onset.

Clinical characteristics of multiple sclerosis with early onset are described. The evolution is frequently relapsing-remitting; compared to the adult form, the EDSS levels of 3, 4 and 6 are reached after a longer interval but at a lower age. Negative prognostic factors are: a short inter-attack interval, a high relapse rate, a relapsing-progressive course or the shift to the secondary progressive phase, and early accumulation of disability.

Disability Evaluation↗
PubMed2004

Devic's neuromyelitis optica: clinical features and prognostic factors.

Devic's neuromyelitis optica (NMO) onset is characterized by optic neuritis (ON) and transverse myelitis (TM), either simultaneously or in isolation. Thereafter, the course of the disease can be monophasic (no other attack) or relapsing (sequences of ON and TM, no other neurological system involved). The risk of having a relapsing course is related to gender, older age at onset, less severe motor impairment after the myelitic onset, interval length between first and second attack. The risk of an unfavourable evolution (severe disability or death) during a relapsing course is mainly related to high relapse rate during the first two years of the disease. In summary, relapsing NMO patients tend to have a poor prognosis, requiring more effective immunosuppressive treatments.

Age of Onset↗
PubMed2004

An unusual case with relapsing neuromyelitis optica associated with undifferentiated connective tissue disease.

A case is presented with attacks of optic neuritis followed by severe myelitis 15 years later, in coincidence with a severe stressful life event. This female patient was also affected by undifferentiated connective tissue disease. This case presents some unusual and atypical findings such as: the association of a relapsing neuromyelitis optica with an undifferentiated connective tissue disease, a very long interval between optic neuritis and myelitis, and the important role of a stressful event in developing a relapse.

Female↗
PubMed2004

Multiple sclerosis and celiac disease: is there an increased risk?

Multiple sclerosis and celiac disease are both considered immune-mediated diseases. Recently, improved serological screening methods provided a higher prevalence of celiac disease (CD) in the general population worldwide and also demonstrated gastrointestinal symptoms may be lacking. The aim of this study was to determine the prevalence of (CD) in an unselected group of 95 adults with multiple sclerosis using transglutaminase antibodies. No patients showed pathological values. Different immune and genetic basis between the two diseases may represent crucial insights to explain our results.

Adult↗