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Biomedical subjects

G Comi

Publications and source records attributed to G Comi.

At least 19 recordsLinked to original sources
PubMed1999

Magnetization transfer imaging of patients with definite MS and negative conventional MRI.

OBJECTIVE: To assess, in a group of patients with clinically or laboratory-supported definite MS and negative conventional MRI scans of the brain, whether magnetization transfer imaging (MTI) is able to detect subtle white matter changes. BACKGROUND: MTI of the brain in patients with MS frequently demonstrates the presence of microscopic damage to white matter, which appears normal on conventional MRI. METHODS: Brain MRI and MTI scans were obtained from 11 patients with negative conventional MRIs of the brain, selected from 618 clinically or laboratory-supported definite MS cases scanned in the last 2 years in three Italian MS centers. RESULTS: Compared with control subjects, patients had significantly lower mean MT ratios (MTR) in the pons, cerebellum, and periventricular regions. The percentages of pixels with MTR values below 1, 2, and 3 SD of the mean MTR value of the control subjects were 7.6% (range, 3.2% to 11.8%), 5.2% (range, 2.0% to 8.5%), and 3.6% (range, 1.2% to 6.1%), respectively. They were mainly located in the white matter of the centra semiovalia, and usually were isolated. CONCLUSIONS: MTI can detect white matter abnormalities in patients with MS and negative conventional brain MRI scans. The detection of such abnormalities may increase diagnostic confidence in those cases where MS is clinically suspected, but conventional MRI does not suggest the diagnosis.

Adolescent↗
PubMed1999

Study on volatile components in salami by reverse carrier gas headspace gas chromatography-mass spectrometry.

Salami are a typical seasoned sausage of Italy; a number of types are produced, according to local traditional recipes. As industrial production has taken place, a number of problems rise in obtaining products similar to the traditional ones. The use of selected microbial starters is permitted by Italian law for some years and at present, microbiological research is engaged in selecting starters similar to the ones isolated from traditional products, with the aim of obtaining organoleptic characteristics close to the ones of traditional recipes. A study was carried out concerning the characterisation of volatile components of salami by headspace capillary gas chromatography-mass spectrometry. As during the sampling step, analytes could reach the analytical column, the carrier gas rate was back flushed in the latter, while a pre column was used as cold trap. Then GC-MS analysis follows. By these techniques, we were able to highlight typical profiles of different salami, as well as monitoring the ripening of a traditional and a starter added salami. Main peaks are of fermentative origin, while also peaks from spices were detected. Ethyl propionate was used as internal standard to be able to normalise the peaks amounts.

Gas Chromatography-Mass Spectrometry↗
PubMed1999

A comparison of the sensitivity of monthly unenhanced and enhanced MRI techniques in detecting new multiple sclerosis lesions.

In this longitudinal study, the sensitivities of three magnetic resonance imaging techniques for detecting the appearance of new lesions in multiple sclerosis (MS) were evaluated and compared. Dual-echo conventional spin-echo (CSE), fast fluid-attenuated inversion recovery (fast-FLAIR) and post-contrast T1-weighted scans were obtained on four occasions, each separated by 28 days, from 18 patients with relapsing-remitting MS using a 1.5-T machine. New lesions seen using each sequence during the follow-up were counted by agreement by four observers in two stages (stage 1: random review of complete sets of scans from each technique; stage 2: side-by-side review with a 'retrospective' count of new lesions). At stage 1, 1.44 new lesions per patient per month were detected on CSE scans, 1.88 on fast-FLAIR (31% more than CSE) and 2.07 on post-contrast T1-weighted scans (44% more than CSE) (P = 0.03). Differences were, however, reduced after stage 2: fast-FLAIR detected 29% and post-contrast T1-weighted scans detected 31% more new lesions than CSE(P = 0.08). The combination of fast-FLAIR and post-contrast scans detected 144 new lesions, whilst the usual combination of CSE and post-contrast scans detected 133 new lesions. This study indicates that enhanced MRI remains the most sensitive method for detecting 'active' lesions in MS and that fast-FLAIR may be used when monitoring short-term disease activity in MS, either natural or modified by treatment.

Adult↗
PubMed1999

Lesion load measurements in multiple sclerosis: the effect of incorporating magnetization transfer contrast in fast-FLAIR sequence.

We compared the ability and reproducibility of a fast fluid-attenuated inversion recovery (fast-FLAIR) sequence with and without a magnetization transfer (MT) pulse for detecting and measuring multiple sclerosis (MS)-related abnormalities on magnetic resonance imaging (MRI) scans from 20 patients. The Contrast-to-Noise ratios between lesions and normal-appearing white matter, lesion numbers, lesion volumes and the variability of such measurements were similar for the two sequences. This suggests that the addition of MT to FLAIR sequences as currently implemented on standard MRI scanners does not improve the detection of MS lesions.

Adult↗
PubMed1999

A longitudinal study comparing the sensitivity of CSE and RARE sequences in detecting new multiple sclerosis lesions.

In this longitudinal study, we evaluated the sensitivities of dual-echo, conventional spin-echo (CSE), and rapid-acquisition relaxation-enhanced (RARE) scans for detecting the appearance of new lesions in multiple sclerosis (MS). Dual echo, CSE, and RARE scans were obtained on four occasions each separated by 28 days from five patients with relapsing-remitting MS using a 1.5-Tesla machine. A total of 44 new lesions were detected by the two sequences. Thirty-five lesions were seen on both sequences, three only on CSE and six only on FSE. This study indicates that CSE may be substituted by RARE when monitoring short-term disease activity in MS.

Brain↗
PubMed1999

Repeatability of surface EMG variables during voluntary isometric contractions of the biceps brachii muscle.

The repeatability of initial value and rate of change of mean spectral frequency (MNF), average rectified values (ARV) and muscle fiber conduction velocity (CV) was investigated in the dominant biceps brachii of ten normal subjects during sustained isometric voluntary contractions. Four levels of contraction were studied: 10%, 30%, 50% and 70% of the maximal voluntary contraction level (MVC). Each contraction was repeated three times in each of three different days for a total of nine contractions/level/subject and 90 contractions per level across the ten subjects. Repeatability was investigated using the Intraclass Correlation Coefficient (ICC) and the standard error of the mean (SEM) of the estimates for each subject. Contrary to observations in other muscles, CV estimates appeared to be very repeatable both within and between subjects. CV showed a small but significant increase when contraction force increased from 10% to 50% MVC but no change for further increase of force. As force increased, MNF showed a slight decrease possibly related to a wider spreading of the CV values. The rate of time decrement of MNF and CV increased with the level of contraction. The normalized decrement (% of initial value per second) was in general higher for MNF than for CV and was more repeatable between subjects at 10% MVC than at 70% MVC. A final observation is that a resting time of 5 minutes may not be sufficient after a contraction at 50% or 70% MVC.

Adult↗
PubMed1999

Inter-laboratory validation of an ELISA for the determination of serum anti-ganglioside antibodies.

Anti-ganglioside antibodies are frequently sought in the sera of patients with autoimmune peripheral neuropathy, using an enzyme-linked immunosorbent assay (ELISA) as the principal method for antibody detection. Wide variations in assay performance between laboratories have been reported. In this study, we established a standardized ELISA method between laboratories within the European Inflammatory Neuropathy Cause and Treatment (INCAT) group and determined the inter-laboratory variance in assay performance using both the standardized INCAT method and in-house local methods. As expected, the inter-laboratory variances were greater using local methods than using the standardized method, producing titre estimates which could be 24.8 or 7.6 times larger or smaller, respectively, than the true means for these laboratories. Using the standardized method, the within laboratory measurement error accounted for 41% of the inter-laboratory variation, providing a theoretical upper limit to which technical improvements within laboratories could reduce inter-laboratory variation. These data describe the intrinsic weaknesses within the widely used ganglioside antibody ELISA methods and reinforce the importance of inter-laboratory cooperation within this area. Standardized serological reagents used in this study are available from INCAT members.

Antibodies↗
PubMed1999

Correlation between MRI and short-term clinical activity in multiple sclerosis: comparison between standard- and triple-dose Gd-enhanced MRI.

We assessed the relative sensitivities of standard (SD)- and triple-dose (TD) gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) for detecting enhancing lesions in different phases of multiple sclerosis (MS) disease activity. Ten MS patients were studied with monthly brain MRI scans for a 3-month follow-up (i.e., 4 scans were obtained for each patient with both SD and TD). A total of 11 relapses were recorded and treated with short-term high-dose steroid therapy. Enhancing lesion numbers and volumes were significantly higher for TD vs. SD scans (p < 0.0001). For both Gd doses, the numbers and volumes of lesions were higher during clinical relapses; the differences were statistically significant when comparing the results for scans obtained during and after a relapse. The gain in sensitivity of TD vs. SD scans for enhancing lesion detection was lower during relapses, whilst it was maximum after relapses, although these differences did not reach statistical significance. Our data confirm the potential role of TD MRI for monitoring MS activity, since, with its higher sensitivity, it may detect more subtle blood-brain barrier (BBB) damage. They also suggest that the degree of BBB damage in individual lesions changes during different phases of disease activity.

Adult↗
PubMed1999

Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI.

OBJECTIVE: To identify differences in pathology between the principal clinical phenotypes of MS using conventional and magnetization transfer (MT) MRI. METHODS: T1-weighted and T2-weighted images as well as MT scans were obtained from 20 controls, 21 patients presenting with clinically isolated syndromes suggestive of MS, and 93 MS patients with relapsing-remitting, secondary progressive, benign, or primary progressive course. Metrics considered: hypointense T1 and T2 lesion volumes, average lesion MT ratio, average brain MT ratio, peak height and position from MT histograms. RESULTS: MS patients had lower MT metrics than controls. Patients with clinically isolated syndromes had MT measures similar to controls, whereas primary progressive MS patients had lower histogram peak height with normal peak position. Relapsing-remitting MS patients had lower MT measures, higher T2 lesion load and ratio of hypointense T1 to T2 lesion volumes than patients with clinically isolated syndromes, and lower MT ratio and peak height than benign MS patients. Benign MS patients were similar to controls and patients with clinically isolated syndromes. Secondary progressive MS patients had the lowest MT measures and highest lesion loads. CONCLUSIONS: Pathology in patients with clinically isolated syndromes is confined to modest tissue damage in the lesions seen on T2-weighted scans. Severe damage is important for the later development of disability. However, microscopic damage in normal-appearing white matter may be a major contributor to disability in primary progressive MS.

Adult↗
PubMed1999

Interscanner variation in brain MR lesion load measurements in multiple sclerosis using conventional spin-echo, rapid relaxation-enhanced, and fast-FLAIR sequences.

BACKGROUND AND PURPOSE: Different MR pulse sequences have been proposed for measuring multiple sclerosis (MS)-related abnormalities. The reproducibility of measured brain MS lesion volumes was compared for MR images performed using different scanners and different pulse sequences. METHODS: Nine patients with relapsing-remitting MS were each imaged on two scanners and, on each occasion, dual-echo conventional spin-echo, dual-echo rapid-acquisition relaxation-enhanced (RARE), and fast fluid-attenuated inversion recovery (fast-FLAIR) images were obtained. The lesion volume present on each image was evaluated three times by a single observer in random order, using a local thresholding technique. RESULTS: The mean lesion volumes present on fast-FLAIR images were significantly higher than those measured on dual-echo conventional spin-echo and RARE images. The mean intraobserver coefficients of variation for the different sequences and scanners ranged from 3.0% to 4.2% (no statistically significant difference). For each of the sequences, the use of different scanners introduced a variability that was higher than the intraobserver variability: the interscanner coefficient of variation was 7.4% for conventional spin-echo, 9.5% for RARE, and 18.5% for fast-FLAIR images. CONCLUSION: Our study confirms that the use of different scanners significantly influences lesion loads measured from MR images of patients with MS and establishes that newer sequences are more susceptible to measurement variability. It also indicates that, if newer sequences are to be used in clinical trials, careful standardization is needed.

Adult↗
PubMed1998

Central nervous system delivery of interleukin 4 by a nonreplicative herpes simplex type 1 viral vector ameliorates autoimmune demyelination.

Multiple sclerosis (MS) is a T cell-mediated organ-specific inflammatory disease leading to central nervous system (CNS) demyelination. On the basis of results obtained in experimental autoimmune encephalomyelitis (EAE) models, MS treatment by administration of antiinflammatory cytokines such as interleukin 4 (IL-4) is promising but is hampered by the limited access of the cytokines to the CNS and by the pleiotropic effects of systemically administered cytokines. We established a cytokine delivery system within the CNS using non-replicative herpes simplex type 1 (HSV-1) viral vectors engineered with cytokine genes. These vectors injected into the cisterna magna (i.c.) of mice diffuse in all ventricular and subarachnoid spaces and infect with high efficiency the ependymal and leptomeningeal cell layers surrounding these areas, without obvious toxic effects. Heterologous genes contained in the vectors are efficiently transcribed in infected ependymal cells, leading to the production of high amounts of the coded proteins. For example, 4.5 ng of interferon gamma (IFN-gamma) per milliliter is secreted into the cerebrospinal fluid (CSF) up to day 28 postinjection (p.i.) and reaches the CNS parenchyma in bioactive form, as demonstrated by upregulation of MHC class I expression on CNS-resident cells. We then exploited the therapeutic potential of the vectors in EAE mice. An HSV-1-derived vector containing the IL-4 gene was injected i.c. in Biozzi AB/H mice at the time of EAE induction. We found the following in treated mice: (1) delayed EAE onset, (2) a significant decrease in clinical score, (3) a significant decrease in perivascular inflammatory infiltrates and in the number of macrophages infiltrating the CNS parenchyma and the submeningeal spaces, and (4) a reduction in demyelinated areas and axonal loss. Peripheral T cells from IL-4-treated mice were not affected either in their antigen-specific proliferative response or in cytokine secretion pattern. Our results indicate that CNS cytokine delivery with HSV-1 vectors is feasible and might represent an approach for the treatment of demyelinating diseases. Advantages of this approach over systemic cytokine administration are the high cytokine level reached in the CNS, the absence of effects on the peripheral immune system, and the long-lasting cytokine production in the CNS after a single vector administration.

Animals↗
PubMed1998

Magnetization transfer ratios of multiple sclerosis lesions with variable durations of enhancement.

We evaluated whether new multiple sclerosis (MS) lesions with variable durations of enhancement have different magnetization transfer ratios (MTR) at the time of their appearance. We scanned ten patients with relapsing-remitting MS every four weeks on four occasions. During each of the monthly sessions, we obtained dual echo, MT and T1-weighted scans. Five minutes after gadolinium-DTPA (Gd) injection, another T1-weighted scan was obtained. We measured the MTR of new enhancing lesions on co-registered quantitative MTR images. During the three-month follow up, 54 new enhancing lesions were seen with a mean MTR value of 33.6% (SD=7.8%). The mean MTR values were 35.3% (SD=7.0%) for lesions enhancing on only one scan and 29.3% (SD=8.6%) for those enhancing on at least two consecutive scans (P=0.01). These results suggest that enhancing lesions in MS have heterogeneous pathological substrates, which may be associated with different durations of the enhancing phase.

Adult↗
PubMed1998

A rapid method for the identification and partial serotyping of Listeria monocytogenes in food by PCR and restriction enzyme analysis.

Two highly specific primers for Listeria monocytogenes were used to yield from foods such as milk, soft cheese and meat, PCR products that were cleaved with the restriction enzyme HindIII. The fragments generated allowed a distinction between two groups of L. monocytogenes serovars: serovars 1/2a and 1/2c cluster in one group and serovars 1/2b, 3b and 4b in the other subgroup. Since this procedure can be completed in 24 h, an epidemiological association between human disease and suspected sources can be rapidly confirmed at the subgroup level in the laboratory.

Animals↗
PubMed1998

A longitudinal brain MRI study comparing the sensitivities of the conventional and a newer approach for detecting active lesions in multiple sclerosis.

Monthly dual-echo spin-echo (SE) and enhanced magnetic resonance imaging (MRI) after the injection of a standard dose (SD) of gadolinium (Gd) is the conventional approach to monitor short-term disease activity in multiple sclerosis (MS). In this study, the sensitivity of this approach in detecting active lesions in MS was compared with that of monthly fast fluid attenuated inversion recovery (FLAIR) scans associated with enhanced MRI after the injection of a triple dose (TD) of Gd. Thirteen patients with relapsing-remitting MS entered the study. Monthly MRI scans were obtained on four occasions in two separate sessions (interval between 12 and 24 h). In one session, dual-echo conventional SE and SD Tl-weighted scans were obtained; in the other, fast-FLAIR and TD Tl-weighted scans. The order of the two sessions was randomized. Three observers counted the number of active lesions detected by each of the two approaches. One hundred and four active lesions were detected by the conventional approach and 199 by the newer approach (average increase per patient = 75%, range = 0-325%). The mean number of active lesions per month per patient was 2.0 for the conventional approach and 3.8 for the new approach (P = 0.004). Scans with active lesions were 34/52 (65%) with the conventional approach and 37/52 (71%) with the new approach. Our data indicate that the combined use of monthly fast-FLAIR and TD enhanced Tl-weighted scans increases the number of active lesions detected on serial MRI scans from patients with MS.

Adult↗
PubMed1998

Quantitative volumetric analysis of brain magnetic resonance imaging from patients with multiple sclerosis.

We compared the volumes of the brain as a whole and of different cerebral structures from patients with multiple sclerosis (MS) and normal subjects. In the patients, we also correlated brain volumes with T2 and T1 lesion loads and disability. A magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of axial 1-mm thick slices and a dual-echo sequence were obtained in 15 patients with relapsing-remitting or secondary progressive MS and 15 sex-, age-, height- and weight-matched normal subjects. The brains and the different cerebral structures studied (cerebral hemispheres, cerebellum and brainstem) were segmented manually by a single observer on the 1-mm MP RAGE scans. The hyperintense lesion volumes seen on dual-echo scans and the hypointense lesion volumes seen on the 1-mm MP RAGE scans were measured using a semi-automated segmentation technique based on local thresholding. Compared to the normal volunteers, patients had significantly lower cerebral (P = 0.008), hemispheric (P = 0.01) and brainstem (P = 0.03) volumes. Cerebral atrophy was detected in seven (47%) MS patients. Patients with brainstem signs had significantly lower mean brainstem volume than the others (P = 0.04). No significant correlations were found between the cerebral volumes and the EDSS scores, the hyperintense lesion volumes and the hypointense lesion volumes. We conclude that cerebral atrophy is a relatively frequent finding in MS, but its relationship with physical disability is modest.

Adult↗
PubMed1998

A one year study of new lesions in multiple sclerosis using monthly gadolinium enhanced MRI: correlations with changes of T2 and magnetization transfer lesion loads.

In this study, 14 patients with either relapsing-remitting or secondary progressive multiple sclerosis (MS) were scanned monthly using gadolinium enhanced magnetic resonance imaging (MRI). At the start of the study and at 1 year follow up, T2-weighted and magnetization transfer (MT) scans were also performed. The correlation between the frequency and extent of enhancement and changes of lesion load over a 1 year period on T2-weighted and MT images were assessed. For all patients, and for the relapsing-remitting patients only, the number and volume of enhancing lesions per month showed no significant correlation with the change between baseline and 1 year follow up of lesion volumes on T2 and MT images. However, strong correlations were found between the number and volume of gadolinium enhancing lesions with changes of T2 (r = 0.93, P = 0.02) and MT (r = 0.82, P = 0.04) lesion loads in patients with secondary progressive MS. Strong correlations were also found between the lesion loads on T2-weighted scans and on MT images both at baseline and at 1 year follow up (r = 0.83, P = 0.003). In addition, the changes in lesion load over 1 year, detected using the two techniques, were moderately correlated (r = 0.51, P = 0.05). This study provides further evidence that the pathological processes in MS are at different stages in relapsing-remitting and secondary progressive MS. It also suggests that the effectiveness of recovery mechanisms within lesions might be one of the major factors responsible for such a difference.

Adult↗
PubMed1998

IL-12 is involved in the induction of experimental autoimmune myasthenia gravis, an antibody-mediated disease.

IL-12 has been shown to be involved in the pathogenesis of Th1-mediated autoimmune diseases, but its role in antibody-mediated autoimmune pathologies is still unclear. We investigated the effects of exogenous and endogenous IL-12 in experimental autoimmune myasthenia gravis (EAMG). EAMG is an animal model for myasthenia gravis, a T cell-dependent, autoantibody-mediated disorder of neuromuscular transmission caused by antibodies to the muscle nicotinic acetylcholine receptor (AChR). Administration of IL-12 with Torpedo AChR (ToAChR) to C57BL/6 (B6) mice resulted in increased ToAChR-specific IFN-gamma production and increased anti-ToAChR IgG2a serum antibodies compared with B6 mice primed with ToAChR alone. These changes were associated with earlier and greater neurophysiological evidence of EAMG in the IL-12-treated mice, and reduced numbers of AChR. By contrast, when IL-12-deficient mice were immunized with ToAChR, ToAChR-specific Th1 cells and anti-ToAChR IgG2a serum antibodies were reduced compared to ToAChR-primed normal B6 mice, and the IL-12-deficient mice showed almost no neurophysiological evidence of EAMG and less reduction in AChR. These results indicate an important role of IL-12 in the induction of an antibody-mediated autoimmune disease, suggest that Th1-dependent complement-fixing IgG2a anti-AChR antibodies are involved in the pathogenesis of EAMG, and help to account for the lack of correlation between anti-AChR levels and clinical disease seen in many earlier studies.

Animals↗