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Biomedical subjects

G Comi

Publications and source records attributed to G Comi.

At least 145 records · Page 8Linked to original sources
PubMed2000

Sensitivity and reproducibility of volume change measurements of different brain portions on magnetic resonance imaging in patients with multiple sclerosis.

The course of multiple sclerosis (MS) can be monitored by measuring changes in brain volume, but consensus is still lacking on the best strategy to be adopted. We compared the reproducibility and sensitivity of volume measurements from different brain portions for detecting changes on magnetic resonance imaging (MRI) in patients with MS. T1-weighted MRI of the brain was performed in 50 patients with relapsing-remitting MS at study entry and after an average follow-up of 18.4 months. Using a semiautomated technique for brain parenchyma segmentation, the volumes of the following brain portions were measured: (a) the whole brain (whole-brain volume, WBV), (b) the seven slices rostral to the velum interpositum (seven-slice volume, SSV), (c) the central slice of the image set (central-slice volume, CSV) and (d) the infratentorial regions (infratentorial-brain volume, IBV). All these measurements were carried out by a single observer and were repeated twice on ten randomly selected scans to test the intra-observer reproducibility using the four strategies. At follow-up there was a significant decrease in all the measures of brain volume (P ranged from 0.002 to < 0.001). The univariate correlations between changes in WBV, SSV, CSV and IBV were all statistically significant, with the exception of that between changes in CSV and IBV; r values ranged from 0.34 (for the WBV/IBV correlation) to 0.80 (for the WBV/SSV correlation). The mean intra-observer coefficient of variations were 1.9% for WBV, 1.5% for SSV, 2.9% for CSV and 2.2% for IBV measurements. The measurement of volume on a portion of brain selectively including the regions in which MS pathology is more diffuse is as reliable and sensitive to disease-related changes as that on the whole brain, with significant time saving for processing.

Adult↗
PubMed2000

MRI and motor evoked potential findings in nondisabled multiple sclerosis patients with and without symptoms of fatigue.

Fatigue is a common symptom of multiple sclerosis (MS) even in the early phases of the disease, when neurological disability is usually still not present. To investigate the pathophysiology of fatigue we compared neurophysiological (motor evoked potentials of the four limbs, MEPs) and brain magnetic resonance imaging (MRI) findings in two groups of nondisabled MS patients, those with (n=15) and those without (n=15) fatigue. Fatigue was assessed by an interview and scored by the Fatigue Severity Scale. The two groups were matched for sex, age, disease duration, Expanded Disability Status Scale score, pyramidal Functional System (FS) score, and depression score. MEPs were abnormal in five patients with fatigue and in one patient without fatigue. A significant association was found between the patient scores on the Fatigue Severity Scale, and the burden of MRI lesions (r=0.5; P< 0.005). Significantly higher parietal lobe (P< 0.05), internal capsule (P< 0.05), and periventricular trigone (P< 0.05) lesion loads were found in patients with fatigue than in those without. Our results agree with a central nervous system origin of fatigue in MS patients. This symptom might be a consequence either of a functional deafferentation of the cortex due to cortico-subcortical interconnection damage or of a demyelination in critical sites of the CNS, such as the cortico-spinal tract.

Adolescent↗
PubMed2000

The prognosis of idiopathic optic neuritis.

We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after acute isolated optic neuritis in 102 patients in a follow-up study (duration 6.5 +/- 2.0 years). The probability of CDMS was 13% after 2 years, 30% after 4 years, 38% after 6 years, and 49% after 8 and 10 years. CDMS occurred in 42 (59%) of 71 patients with brain lesions detected with magnetic resonance imaging (MRI). No patient with normal MRI exam developed the disease. Patients with 3 or more MRI-detected lesions presented a shorter first interattack interval and a higher relapse rate compared to subjects with only 1 or 2 lesions. The predictive value of CSF examination and of evoked potentials was poor.

Adult↗
PubMed2000

Immunological markers in multiple sclerosis.

Multiple sclerosis (MS) is characterized by the presence in the central nervous system (CNS) of perivascular inflammatory infiltrates containing, among others, autoreactive T cells and activated macrophages. These observations indicate that MS is a T cell-mediated CNS-confined chronic inflammatory demyelinating disease in which the ultimate effector cell is the activated macrophage. The inflammatory process, leading to patchy demyelination and axonal loss, is mainly sustained by pro-inflammatory cytokines that, along with chemokines, adhesion molecules and metalloproteases, modulate at different levels the pathogenic process underlying MS. Due to their central role in MS pathogenesis, "inflammatory" molecules might represent suitable peripheral markers of disease (disease-trait) and/or disease activity (state-trait). However, reliable disease-trait or state-trait immunological markers for MS have not yet been identified. The intrinsic characteristics of these molecules (i.e. autocrine/paracrine activity, short half-life, redundancy) may in part explain their inconsistency as disease markers. Additionally, the unreliability of methodologies and the lack of careful patient stratification can also, at least in part, account for the unsatisfactory results so far obtained.

Biomarkers↗
PubMed2000

Evoked potentials in monitoring multiple sclerosis.

The usefulness of evoked potentials (EPs) in the diagnosis of multiple sclerosis is limited by its relatively low sensitivity to subclinical lesions. However, they are still a good tool to assess the integrity of afferent and efferent pathways and to quantify the severity of white matter involvement. Transversal and longitudinal studies have demonstrated good correlation between EP abnormalities and disability, suggesting that multimodal evoked potentials could be useful in monitoring the disease evolution in single patients and as surrogate end points in clinical trials.

Brain↗
PubMed2000

Prognosis-modifying therapy in multiple sclerosis.

The neurologist's views on disease therapy have changed over recent years from nihilism to reasonable optimism, thanks to the development of MS-specific therapies (interferon beta and COP-1) and to the remarkable advances in the understanding of the pathogenesis of the disease. Available immunological, clinical and pathological data suggest that the early treatment of RRMS patients with immunomodulatory drugs could be more advantageous compared to treatment started later in the disease course. The early reduction of relapse rate as well as of the extent of pathological lesions, should be the strategy for patients particularly in the first phases of the disease. Early treatment has a robust rationale both in prevention of irreversible pathological changes and in reducing clinical and MRI activity with favorable prognostic implications. For the near future, interferon beta and COP-1 seem to be the pharmacological agents best qualified to be utilized for this purpose.

Central Nervous System↗
PubMed2000

Cognitive function and neurophysiological evaluation in early-treated hypothyroid children.

In this study, we assessed cognitive function and neurophysiological development in congenitally hypothyroid (CH) children. We performed a cross-sectional study at the outpatient Pediatric Clinic and Department of Neurophysiology at San Raffaele Hospital, Milan. The study enrolled 25 CH patients (6.00-10.83 years of age) detected by neonatal screening, and 34 healthy control children (4-11 years of age). Patients and controls had comparable scores at neuropsychological tests (WISC-R), and at auditory P300 tests. In contrast, we found significantly longer LLSEP latencies in CH patients (p < 0.03). CH patients treated 30 days after birth showed lower scores at neuropsychological tests, but not at neurophysiological tests, compared to patients who started the replacement therapy earlier. Patients with more severe fetal hypothyroidism (T4 levels at diagnosis < or = 2 micrograms/dl) had lower neuropsychological scores, and similar neurophysiological results, compared with patients with moderate fetal hypothyroidism. The severity of fetal hypothyroidism and early treatment influence the mental outcome of CH patients. Neurophysiological results show that central nervous system damage occurs in some patients despite early treatment.

Child↗
PubMed2000

The SMile Card: a computerised data card for multiple sclerosis patients. SMile Card Scientific Board.

The SMile Card was developed as a means for computerising clinical information for the purpose of transferability, accessibility, standardisation and compilation of a national database of demographic and clinical information about multiple sclerosis (MS) patients. In many European countries, centres for MS are organised independently from one another making collaboration, consultation and patient referral complicated. Only the more highly advanced clinical centres, generally located in large urban areas, have had the possibility to utilise technical possibilities for improving the organisation of patient clinical and research information, although independently from other centres. The information system, developed utilising the Visual Basic language for Microsoft Windows 95, stores information via a 'smart card' in a database which is initiated and updated utilising a microprocessor, located at each neurological clinic. The SMile Card, currently being tested in Italy, permits patients to carry with them all relevant medical information without limitations. Neurologists are able to access and update, via the microprocessor, the patient's entire medical history and MS-related information, including the complete neurological examination and laboratory test results. The SMile Card provides MS patients and neurologists with a complete computerised archive of clinical information which is accessible throughout the country. In addition, data from the SMile Card system can be exported to other database programs.

Europe↗
PubMed2000

Detection of multiple sclerosis lesions using EPI-FLAIR images.

Fast fluid-attenuated inversion recovery (fast-FLAIR) sequences are very sensitive for detecting lesions of patients with multiple sclerosis (MS). Echo planar imaging allows to obtain FLAIR images (EPI-FLAIR) with significantly shorter scanning times. EPI-FLAIR images obtained with 10 measurements are as sensitive as fast-FLAIR for the detection of large MS lesions. Aim of this study was to compare the numbers of MS lesions seen on EPI-FLAIR images with fewer measurements (and, as a consequence, very short scanning times) with those seen on EPI-FLAIR images with 10 measurements. EPI-FLAIR scans with 2 (EPI-2), 4 (EPI-4), 6 (EPI-6), 8 (EPI-8) and 10 (EPI-10) measurements were obtained from 29 MS patients. Lesions seen using each of the five approaches were counted by agreement by two observers. EPI-10 images were used as the "gold standard" for pairwise comparisons. EPI-FLAIR scans with fewer measurements (EPI-2, -4, -6, -8) were all significantly less sensitive than EPI-10 for the detection of small, intermediate and large MS lesions. All the EPI-FLAIR scans, however, fulfilled MR diagnostic criteria for definite MS. When rapid MR scanning of uncooperative MS patients is needed, EPI-FLAIR images covering the entire brain in less than one minute may be considered.

Adult↗
PubMed2000

Loss of Dp140 regulatory sequences is associated with cognitive impairment in dystrophinopathies.

Mental retardation is a clinical feature present in both Duchenne and Becker muscular dystrophy patients and its pathogenesis is still unknown. Dp140 is a dystrophin isoform with predominant expression during foetal brain development. Its promoter and first exon lie in the large intron between exon 44 and 45, a region that is commonly deleted in dystrophinopathic patients. We performed neuropsychological evaluation and genetic analysis of the Dp140 transcription unit on 12 Duchenne muscular dystrophy and 28 Becker muscular dystrophy patients carrying deletions in this critical region. Comparison of neuropsychological and molecular data showed that there is a statistically significant relationship between the loss of Dp140 transcription unit and mental retardation in Becker muscular dystrophy patients (P = 0.008). Such a correlation is not evident in Duchenne muscular dystrophy patients but only shows a trend towards significance (P = 0.063). It is worth noting that both Duchenne muscular dystrophy and Becker muscular dystrophy patients with normal intelligence do not show deletions in the Dp140 regulatory regions. In the light of these findings, we suggest that impairment of cognitive abilities in Duchenne muscular dystrophy and Becker muscular dystrophy patients might be related to a dysfunction of Dp140 brain isoform.

Adolescent↗
PubMed2000

Biochemical responses in a Candida famata strain adapted to high copper concentrations.

A strain of Candida famata adapted to high copper concentration (1.26 mM) and a number of biochemical parameters have been tested, in order to get information on the mechanisms of metal toxicity and detoxification as well as on the metabolic responses to the treatment. The cytoplasmic levels of superoxide dismutase, peroxidase and glutathione were found significantly increased with respect to control cells, in contrast to catalase which is not affected. The activities of enolase and of triosephosphate isomerase are found to decrease as a consequence of the exposure to copper. Statistically significant differences in the content of some aminoacids are found between copper-treated and control cells.

Adaptation, Physiological↗
PubMed2000

Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group.

In this 'double-blind', randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing-remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.

Dose-Response Relationship, Drug↗
PubMed2000

Cytokine gene therapy of autoimmune demyelination revisited using herpes simplex virus type-1-derived vectors.

The peripheral delivery of drugs in patients affected by central nervous system (CNS)-confined diseases is therapeutically ineffective due to the presence of the blood-brain barrier which forms an inaccessible wall to the majority of CNS targeting molecules. When molecules with an anti-inflammatory profile have been systemically administered to patients affected by a chronic inflammatory demyelinating disease of the CNS, such as multiple sclerosis (MS), results have been disappointing. A successful therapeutic approach in MS should therefore consider the delivery of anti-inflammatory molecules directly into the CNS in order to inhibit blood-borne CNS-confined mononuclear cells which act as ultimate effector cells directly destroying oligodendrocytes and/or releasing myelinotoxic substances. Biological and physical vectors engineered with heterologous genes coding for immunomodulatory cytokines with an anti-inflammatory profile might represent the appropriate tool to deliver therapeutic genes into the CNS of patients with MS. So far, cytokine gene therapy has never been attempted in MS, but encouraging results have been obtained in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), using viral vectors or plasmids engineered with cytokine genes and then injected systemically, either in the blood stream or circulating encephalitogenic T cells, or into the CNS. Here, we critically discuss the various attempts made in EAE using gene therapy protocols based on the delivery of immunomodulatory cytokine genes. Special emphasis is put on the use of non-replicative herpes simplex type-1 (HSV)-derived vectors engineered with the gene of the immunomodulatory cytokine interleukin (IL)-4.

Animals↗
PubMed2000

Development of a rapid method for the identification of Lactobacillus spp. isolated from naturally fermented italian sausages using a polymerase chain reaction-temperature gradient gel electrophoresis.

A rapid method for the identification of Lactobacillus spp. isolated from naturally fermented Italian sausages was developed. It is based on the amplification of a small fragment from the 16S rRNA gene followed by temperature gradient gel electrophoresis (TGGE). Lactobacillus sakei, L. curvatus, L. alimentarius, L. casei, L. plantarum and L. brevis, obtained from International Collections, were used to optimize the method. Thiry-nine strains of Lactobacillus spp. were isolated from naturally fermented sausages and, after traditional identification, were tested by the PCR-TGGE protocol developed. No differences were observed comparing the results obtained, apart from five strains identified as L. curvatus that showed a PCR-TGGE profile identical to L. sakei.

Bacterial Typing Techniques↗
PubMed2000

A multiplex-PCR method to detect enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli in artificially contaminated foods.

In view of the considerable public health risk of the enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli, a multiplex-PCR based method was used for the amplification of the slt genes and of the eaeA gene. Three pairs of primers, different from the oligonucleotides previously used by other authors, were exploited for the amplification. Different E. coli serotypes were tested with the optimized protocol. Fifty three artificially contaminated samples and sixty naturally contaminated samples were processed with the multiplex-PCR. All the artificially contaminated samples gave positive results independently of the number of cells inoculated. On the contrary, the naturally contaminated samples were all negative. The results obtained from this experiment demonstrated that this protocol could be used for monitoring the spread of these organisms in food.

DNA Primers↗
PubMed2000

Computer-assisted EEG monitoring during carotid endarterectomy.

The purpose of this study was to develop a reliable method of EEG analysis during carotid endarterectomy. EEGs of 104 patients under general anesthesia were processed by three different methods: a) "on-line" visual analysis during surgery, b) "off-line" visual analysis in laboratory, and c) computer analysis. To identify pathological EEGs, variability and asymmetry indexes of the 0.5-3.5 Hz and 8-15 Hz bands, absolute power and variability indexes of spectral edge frequency (SEF), and main dominant frequency were evaluated. On-line visual analysis showed clamp-related modifications in 29 EEGs (27.9%). Off-line visual analysis detected 24 pathological EEGs (23.1%): 18 with major changes and 6 with moderate changes. Computer analysis showed 21 EEGs (20.19%) with at least one altered index and 7 (6.7%) with altered variability for both SEF and 8-15 Hz power. The statistical analysis was significant for SEF variability and for 8-15 Hz power variability and asymmetry (P < 0.0001, analysis of variance test). While SEF and 8-15 Hz power variability did not appear influenced by anesthesia and single electrode artifacts, 8-15 Hz power asymmetry index was confounded by the presence of contralateral internal carotid occlusion. The data show that the use of these spectral indexes adds objective information to visual analysis, supporting and making easier intraoperative strategies. Their routine clinical use does not involve additional costs remaining technical requirements unchanged compared to traditional recording.

Aged↗
PubMed2000

Why treat early multiple sclerosis patients?

Class 1 clinical trials demonstrated that immunomodulatory treatments (interferon beta and glatiramer acetate) reduce the disease activity and the accumulation of disability in relapsing remitting multiple sclerosis. Moreover interferon beta-1b also had similar positive effects in secondary progressive multiple sclerosis. The magnitude of these clinical effects was modest, but the reduction of inflammatory activity, as revealed by magnetic resonance imaging, was marked. Converging evidence from new pathological studies and new magnetic resonance techniques, characterized by increased pathological specificity, has shown that already in the early phases of the disease inflammatory activity determines irreversible axonal damage. Moreover, the amount of inflammatory activity at the clinical presentation of the disease has some value in predicting long-term disability. Taken together, these data indicate that patients may benefit from early treatment; the positive results of the Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study support this conclusion.

Adjuvants, Immunologic↗