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Biomedical subjects

G Comi

Publications and source records attributed to G Comi.

At least 289 records · Page 16Linked to original sources
PubMed1996

Brain and spinal cord MR in benign multiple sclerosis: a follow-up study.

We performed a clinical and magnetic resonance (MR) longitudinal study in 19 patients with benign multiple sclerosis (MS) to achieve a better definition of the nature of disability in MS. Patients with higher lesion volumes on conventional T2-weighted images at entry were those with more frequent relapses (p = 0.0004) and more new MR lesions (p = 0.003) during the follow up. However, 1/3 of these new lesions were located periventricularly and about 2/3 were small or intermediate in size. Two of the 11 patients (18%) with higher lesion volumes at entry developed progressive neurological deficits: in these two patients the new lesions seen on conventional T2 images had lower magnetization transfer ratios (p = 0.005) than those present in patients who remained clinically stable and a marked increase in hypointense lesion volumes on T1-weighted images was also found. Spinal cord cross-sectional area at C5 and MTR values for the seemingly normal white matter were similar to those found in normal controls. This study suggests that patients with benign MS have two different patterns of disease evolution, one characterized by very low clinical and MR activities, the other in which the lack of disabling symptomatology might be related to factors like site, size and nature of lesions. It also indicates that in patients with benign MS and high MR lesion loads the risk of developing a secondary progressive form of the disease is still present even after many years after onset.

Adult↗
PubMed1996

Quantitative assessment of MRI lesion load in multiple sclerosis. A comparison of conventional spin-echo with fast fluid-attenuated inversion recovery.

In this study, we compared a fast fluid-attenuated inversion recovery (fast-FLAIR) sequence to conventional spin-echo (CSE) in the evaluation of brain MRI lesion loads of seven patients with clinically definite multiple sclerosis. Interleaved CSE (3000/20, 5 mm contiguous axial slices) and fast-FLAIR (9000/150/2200, 5 mm contiguous axial slices) sequences were performed on a 1.0 T machine. Lesions were counted consensually by two observers and then segmented independently by two other observers using a local thresholding technique, with subsequent manual editing in the case of poorly defined lesions. Four hundred and two lesions were detected in at least one of the two sequences: 128 were seen only on fast-FLAIR, 17 only on CSE. Forty-one lesions were larger on fast-FLAIR, while no lesion was considered larger on CSE. The numbers of periventricular (P = 0.05), cortical/subcortical (P = 0.02) and discrete (P = 0.05) lesions detected using fast-FLAIR were higher than those detected using CSE. The median lesion load was 7185 mm3 on CSE and 8418 mm3 on the fast-FLAIR, the average being 18% (range = 11.6-29%) higher on the fast-FLAIR images. Lesion contrast ratio was higher for lesions on the fast-FLAIR than on the CSE sequence (P < 0.0001). The percentages of poorly defined lesions which needed manual editing after the local thresholding technique was applied and the total time needed for the measurements were lower (P < 0.001) when fast-FLAIR images were used compared with CSE. This resulted in a reduced inter-rater coefficient of variation in measuring lesion volumes. Our data indicate that fast-FLAIR sequences are more sensitive than CSE in detecting multiple sclerosis lesion burden and that fast-FLAIR is a promising technique for natural history studies and clinical trials in multiple sclerosis.

Adult↗
PubMed1996

A combined polymerase chain reaction and restriction endonuclease enzyme assay for discriminating between Campylobacter coli and Campylobacter jejuni.

A combined polymerase chain reaction and restriction endonuclease (RE) enzyme assay was developed to discriminate between Campylobacter coli and Campylobacter jejuni. Amplimers of the FlaA gene obtained by PCR were digested with AluI and HinfI to distinguish C. coli from C. jejuni. With AluI digestion C. jejuni-specific bands were observed at 110, 140 and 160 bp and C. coli-specific bands at 293 and 147 bp. C. jejuni-specific bands of 349 and 109 bp were found by HinfI digestion but HinfI did not digest the FlaA amplimer of C. coli. This combined technique is fast and easy to perform, and distinguishes the two campylobacters unequivocally.

Campylobacter coli↗
PubMed1996

Semi-automated thresholding technique for measuring lesion volumes in multiple sclerosis: effects of the change of the threshold on the computed lesion loads.

Quantitative evaluation of lesion load in multiple sclerosis (MS) from magnetic resonance imaging (MRI) scans is becoming important in understanding and monitoring the progression of the disease. Methods of MS lesion segmentation based on intensity thresholding offer one of the most robust and easily-implemented means of computing the total lesion volume. This study evaluated the effects of slight changes in the choice of intensity threshold on computed lesion volumes in 20 patients with MS using such a technique. After judging the optimum choice of threshold value, the threshold value was increased and decreased by 3% in 1% steps around this value; we observed a mean change of 15% in computed lesion volumes for 1% changes of threshold value. Larger changes in lesion volume were found when the threshold was changed by larger amounts. On the other hand, the amount of time required for manual review decreased, and the confidence with which manual review could be performed increased when using lower thresholds. This study shows that the choice of threshold is a crucial factor in measuring lesion volumes in MS when using intensity-based techniques. It also suggests that in multicenter and/or longitudinal studies, criteria for choosing the threshold should be developed whereby the threshold level should be set such that all MR visible lesions are above it, in order to minimise the human interaction and, consequently, the reproducibility of the results.

Brain↗
PubMed1996

Correlation between brain MRI lesion volume and disability in patients with multiple sclerosis.

In this study we evaluated the relationships between clinical variables and lesion volumes measured from magnetic resonance imaging (MRI) scans in a large cohort of multiple sclerosis (MS) patients. One hundred and thirty patients with MS entered the study: 36 patients had relapsing-remitting (RR), 39 benign (B), 42 secondary progressive (SP) and 13 primary progressive (PP) courses. There was a significant correlation (r = 0.3; p = 0.0006) between the total lesion load and the EDSS score when the whole cohort of patients was considered. This correlation increased (r = 0.5) when only patients with RRMS and SPMS were considered. Our data indicate that a correlation between disability and MRI lesion volume in MS exists, but its strength is moderate.

Adult↗
PubMed1996

Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis.

OBJECTIVES: To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS: T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS: Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS: More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous.

Gadolinium DTPA↗
PubMed1996

Interferon-gamma activated calcium influx in peripheral blood lymphocytes from patients with primary and secondary progressive multiple sclerosis.

Interferon-gamma (IFN-gamma) contributes to the early events leading to T cell activation in relapsing-remitting (RR) multiple sclerosis (MS) by activating a transplasmalemma calcium influx, the detection of which is closely associated with clinical and MRI evidence of disease activity. The appearance of this influx represents one of the earliest peripheral events in the pathogenesis of RRMS. It is still questioned whether the same immune mediated mechanisms also operate in primary progressive (PP)MS. Fluorimetric evidence of the IFN-gamma activated calcium influx was sought in 16 patients with PPMS and 39 patients with secondary progressive (SP)MS. To compare peripheral versus CNS evidence of immune activation 11 of the patients with PPMS and 27 of the patients with SPMS underwent gadolinium enhanced brain MRI. The IFN-gamma activated influx was detected in peripheral blood lymphocytes from eight of 16 (50%) patients with PPMS, and 20 of 39 (51%) patients with SPMS, a frequency similar to that previously reported in patients with RRMS during phases of disease stability. Gadolinium enhancing brain MRI lesions were found in only one of 11 (9%) patients with PPMS and 12 of 27 (41%) with SPMS. Our study shows that peripheral blood lymphocytes from patients with PPMS and patients with SPMS express with the same frequency as patients with RRMS, an IFN-gamma dependent intracellular process leading to T cell activation able to trigger disease activity.

Adult↗
PubMed1996

Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with MS.

We studied whether a triple dose of gadolinium-DTPA alone or in combination with delayed scanning increases the sensitivity of brain MRI for detecting enhancing lesions in patients with MS. We obtained T1-weighted brain MRI scans in two sessions for 22 patients with clinically definite MS. In the first session, we obtained one scan 5 to 7 minutes after the injection of 0.1 mmol/kg gadolinium-DTPA (standard dose). In the second session, 6 to 24 hours later, we obtained one scan before the two scans 5 to 7 minutes (for all patients) and one hour (for 11 patients) after the injection of 0.3 mmol/kg gadolinium-DTPA (triple dose). We detected 83 enhancing lesions in 14 patients when the standard dose of gadolinium-DTPA was used. The numbers of enhancing lesions increased to 138 (average increase 66%; p = 0.001) and the numbers of patients with such lesions to 18 (increase 28%) when we used the triple dose of gadolinium-DTPA. In addition, the total area per patient occupied by such lesions was greater (p < 0.0001) and lesion signal intensity higher (p = 0.0001) on the triple-dose scans than the standard-dose scans. There was an increase in the number of large enhancing lesions (p = 0.03) in the scans obtained 1 hour after the injection of the triple dose of gadolinium-DTPA. These data indicate that in patients with MS, a triple dose of gadolinium-DTPA can reveal many more enhancing lesions, which also appear larger. This suggests that the pathologic nature of "active" lesions in MS is heterogeneous, which might have impact on planning clinical trials.

Contrast Media↗
PubMed1996

Clinical and radiologic correlates of a novel T lymphocyte gamma-interferon-activated Ca2+ influx in patients with relapsing-remitting multiple sclerosis.

T lymphocytes are the main cellular mediators in MS pathogenesis, and their activity is modulated by a complex cytokine network in which gamma-interferon (gamma-IFN) is considered essential. We have recently identified a new transplasmalemma Ca2+ influx activated by gamma-IFN in T lymphocytes (mainly CD4+) from patients with MS that makes T cells more susceptible to proliferation. To define the possible role of this Ca2+ influx as a marker of disease activity, we correlated its appearance with clinical and MRI findings in a cross-sectional study of 67 patients with relapsing-remitting MS (RR-MS). We also conducted a short-term longitudinal evaluation (every 15 days over a 5- to 7-month period) in three of the RR-MS patients. Sixty-five percent of all clinically active RR-MS patients showed the gamma-IFN-activated Ca2+ influx. However, positivity was higher in the first week (78%) after the onset of a clinical exacerbation than the second (57%) and third (44%) weeks. The influx was also detected in 45% of clinically stable RR-MS patients, 30% of RR-MS patients with a "benign" course of the disease, 14% of the other active autoimmune or neurologic disease patients, and 9% of healthy subjects (RR-MS versus control subjects, p < 0.001). Brain-MRI gadolinium-enhancing lesions were more frequently found in influx-positive (72%) than in influx-negative (47%) patients (p < 0.005). In the longitudinal study, we recorded five intracellular Ca2+ ([Ca2+]i) elevations and three clinical attacks (one per patient). A peak increase of [Ca2+]i due to the gamma-IFN-activated Ca2+ influx always preceded the clinical attacks from 4 to 45 days and coincided to MRI evidence of inflammation. [Ca2+]i had returned to baseline levels by the time of the onset of two clinical attacks. This finding may account for the lack of detection of the gamma-IFN-activated Ca2+ influx in some RR-MS patients during the first week after clinical onset. The strong association between the influx and clinical and MRI evidence of disease activity supports its role in the early phases of cellular immune activation leading to demyelination in MS. The detection of [Ca2+]i elevations due to the gamma-IFN-activated Ca2+ influx may represent a valuable prognostic marker of disease activity and may be useful to monitor immunologic studies of MS patients in future clinical trials.

Adolescent↗
PubMed1996

An autosomal locus predisposing to multiple deletions of mtDNA on chromosome 3p.

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more respiratory-chain enzymes carrying mtDNA-encoded subunits. The pattern of inheritance indicates a nuclear gene defect predisposing to secondary mtDNA deletions. Recently, in one Finnish family, we assigned an adPEO locus to chromosome 10q 23.3-24.3 but also excluded linkage to this same locus in two Italian adPEO families with a phenotype closely resembling the Finnish one. We applied a random mapping approach to informative non-10q-linked Italian families to assign the second locus for adPEO and found strong evidence for linkage on chromosome 3p 14.1-21.2 in three Italian families, with a maximum two-point lod score of 4.62 at a recombination fraction of .0. However, in three additional families, linkage to the same chromosomal region was clearly absent, indicating further genetic complexity of the adPEO trait.

Adult↗
PubMed1996

Analysis of temporal non-stationarities in EEG signals by means of parametric modelling.

A method for the analysis of variability of EEG signals is described. We examined simulated signals and real EEGs obtained from a normal subject and two epileptic patients. The first step of the method is based on autoregressive (AR) modelling of short EEG epochs. Prediction coefficients of the AR model were computed as a function of time from partially-overlapping moving windows of 2 s duration. The temporal behaviour of these coefficients was analysed to detect variability: quasi-stationary activity causes only smooth changes in the coefficients while variations in the amplitude and/or the frequency content of the signal are shown to produce sharp changes in the coefficients. A segmentation algorithm was developed to detect and quantify with a numerical value (Difference Measure, DM) the AR coefficients variations.

Algorithms↗
PubMed1995

Searching for genes affecting the structural integrity of the mitochondrial genome.

Mendelian traits associated with qualitative or quantitative abnormalities of mtDNA are presumably caused by mutations in nucleus-encoded genes that deleteriously interact with the mitochondrial genome. Qualitative abnormalities of mtDNA are typically represented by pleioplasmic multiple mtDNA deletions, that are detected in stable tissues, including skeletal muscle, of patients affected by Autosomal Dominant Chronic Progressive External Ophthalmoplegia. Quantitative abnormalities are represented by tissue-specific depletion of mtDNA, associated with different clinical presentation in infancy or childhood. Linkage analysis and search for candidate genes are two complementary strategies aimed at identifying the genes responsible for these disorders.

Animals↗
PubMed1995

Resolution-dependent estimates of lesion volumes in magnetic resonance imaging studies of the brain in multiple sclerosis.

In this study, we investigated the relationship between multiple sclerosis lesion volumes measured from magnetic resonance imaging scans and image-slice thickness. The lesion volume was computed using a semiautomated thresholding technique from axial scans of the brain of varying slice thickness. Ten patients were studied, and in all cases the computed lesion volume increased with decreasing slice thickness (p = 0.01). Linear extrapolation from our data allowed the lesion volume at very small slice thickness to be estimated; this was found to be on average 20% greater than that obtained using a slice thickness of 5 mm. Furthermore, there were considerable differences in the percentage of change in lesion volume from patient to patient, and it would appear that there is a larger variation with slice thickness for patients with smaller lesions and higher lesion loads.

Adult↗
PubMed1995

High serum creatine kinase levels associated with cylindrical spirals at muscle biopsy.

We studied the muscle biopsy from an asymptomatic patient with high serum creatine kinase values. Subsarcolemmal and intermyofibrillar granular inclusions were seen at the light microscopy level. Ultrastructural observation showed clusters of cylindrical spirals (CS). CS are nonspecific, morphological finding, so far reported only in a few cases, presenting with a wide variety of clinical phenotypes. The case we describe is peculiar because of the complete lack of clinical symptoms. The nature of the CS is unknown; we studied a possible alteration of cytoskeletal proteins using a set of different antibodies against these structures, but none of them reacted with CS. Also, since CS have been described in association with mitochondrial abnormalities, and since in our case CS were strongly positive when stained for succinate dehydrogenase, we performed specific immunohistochemical and genetic studies which ruled out any major mitochondrial alterations.

Adult↗