Search PubMed⌕ Search

Biomedical subjects

G Comi

Publications and source records attributed to G Comi.

At least 271 records · Page 15Linked to original sources

Sensitivity of delayed gadolinium-enhanced MRI in multiple sclerosis.

INTRODUCTION: We performed this study to define the sensitivity of delayed gadolinium-enhanced magnetic resonance imaging (MRI) in detecting active lesions in the brains of patients with multiple sclerosis (MS). MATERIAL AND METHODS: T1-weighted images were obtained in 27 patients with relapsing-remitting or secondary progressive MS before, 5-7 min and 20-30 min after the injection of 0.1 mmol/kg gadolinium-DTPA. RESULTS: One-hundred-and-three enhancing lesions were found on the early and 110 on the delayed scans (increase=6.4%). Six patients had 8 additional lesions in the delayed scans, while 1 patient had 1 more lesion on the early scan. Two of the 12 (17%) patients with no enhancing lesions on the early scans had 2 enhancing lesions on the delayed scans. The average increase of enhancing lesion detection with delayed scanning was 14.5% for those patients who already had enhancing lesions on the early post-contrast scans. A significant increase of the enhancing lesion volume was found with delayed scanning (P=0.004). CONCLUSION: These data indicate that it is possible to increase MRI sensitivity in detecting MS active lesions by delaying the scanning after gadolinium injection.

Adult↗

A longitudinal magnetic resonance imaging study of the cervical cord in multiple sclerosis.

This study was performed to evaluate the correlation between changes of cross-sectional cord area and disability in multiple sclerosis. Axial magnetic resonance images at the C-5 spinal level were obtained at entry and 12 months later for 29 patients with clinically definite multiple sclerosis. The degree of disability was inversely correlated at entry and follow-up with the cross-sectional area and the transverse diameter of the spinal cord. In addition, changes in disability correlated inversely with changes in cross-sectional area (r = -0.4, p = 0.04). These findings suggest that cross-sectional cord area at C-5 might be a useful marker of disease evolution.

Adult↗

Interferon-gamma induced increases in intracellular calcium in T lymphocytes from patients with multiple sclerosis precede clinical exacerbations and detection of active lesions on MRI.

BACKGROUND: Interferon (IFN)-gamma exerts a multiplicity of actions potentially relevant for the pathogenesis of multiple sclerosis, including the expression of a transplasmalemma calcium (Ca2+) influx leading to an intracellular Ca2+ ([Ca2+]i) increase able to lower T lymphocyte threshold of excitability. It has been previously shown in a cross sectional cumulative study that this influx is associated with clinical and MRI evidence of disease activity. METHODS: To evaluate the temporal relation between disease activity and the IFN-gamma activated Ca2+ influx in individual patients, a fluorimetric analysis was performed on peripheral blood lymphocytes from eight patients with relapsing-remitting multiple sclerosis every 15 days for one year. RESULTS: Fluctuations of the influx were correlated with clinical events and monthly enhanced brain MRI. The influx was detected a mean of 10.4 (range 7-17) times per patient during our analysis. In 61% of the occasions, influx induced [Ca2+]i increases were recorded in each patient in more than two consecutive measurements, determining sustained [Ca2+]i increases lasting for a mean of 31.5 days. Peak [Ca2+]i increases preceded clinical attacks (P=0.04) or maximal detection of brain MRI enhancing lesions (P=0.05) by a mean of 30.8 and 34.2 days respectively. Spectral analysis of time series further indicated that the fluctuation frequency of [Ca2+]i increases due to the influx over time were superimposable on the appearance of new MRI lesions in all patients and confirmed that in two thirds of the patients these [Ca2+]i increases occurred significantly before (P<0.005) or concurred with new lesion appearance. Finally, the overall presence of the influx throughout the follow up period correlated (P=0.03) with the patients' exacerbation rates. CONCLUSIONS: Intracellular events leading to T lymphocyte activation in multiple sclerosis occur in the peripheral blood before CNS specific events become evident and are, in part, sustained by cytokine induced Ca2+ mediated phenomena.

Adult↗

Intravenous immunoglobulin treatment in multifocal motor neuropathy and other chronic immune-mediated neuropathies.

This review deals with the use of intravenous IVIg immunoglobulins in the treatment of chronic immune-mediated neuropathies: multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy, neuropathies associated with monoclonal gammopathies. A particular attention is given to case series and trials which compare IVIg to other therapies, such as steroid treatment immunosuppressors and plasma exchange. At present clinical and instrumental data seem to indicate the short term efficacy of IVIg in multifocal motor neuropathies, especially as early treatment; further studies are need in order to prove its long term efficacy in this disease. Concerning chronic inflammatory demyelinating polyneuropathies, short term IVIg efficacy is comparable to that of plasma exchange and in the long term most patients need repeated treatments. Most patients respond to the initial therapy and the initial nonresponders usually improve with a second treatment modality.

Autoimmune Diseases↗

The influence of slice orientation on brain MRI lesion load measurement in multiple sclerosis.

This study aimed at evaluating the influence of a different slice orientation on brain magnetic resonance imaging (MRI) lesion load in multiple sclerosis (MS). Fifteen MS patients were scanned obtaining both axial and sagittal conventional spin echo (24 slices; TR 2400, TE 30/80) brain MRI. The total lesion load (TLL) was assessed twice for each scan, using a semi-automated local thresholding technique and the same marked hardcopies. The mean TLL was 22734 mm3 for axial and 22003 mm3 for sagittal scans. The mean intra-observer coefficient of variation (COV) was 4.65% for the axial acquisitions and 4.52% for the sagittal acquisitions. This difference was not statistically significant (one-way ANOVA, P > 0.1). The lesion load was significantly higher from axial MRI as compared to the intra-observer variability (two-way ANOVA, P=0.01), but the fluctuations around this average difference between axial and sagittal scan TLL were significantly large (test for interaction, P < 0.001). Our data indicate that the use of sagittal conventional MRI scans does not seem to be worthwhile for the quantitative assessment of lesion load in MS patients.

Adult↗

The effect of imprecise repositioning on lesion volume measurements in patients with multiple sclerosis.

In this study, we evaluated the effect of imprecision in patient repositioning encountered in real life on multiple sclerosis (MS) lesion volumes measured from MRIs. We also evaluated two putative methods for reducing the variability in these lesion volume measurements: first, a reduction of slice thickness (from the conventional 5 mm to 3 mm) and second, the application of a new repositioning technique based on the use of head immobilization shells. We evaluated the errors in lesion volume by scanning 10 patients a total of four times using the two slice thicknesses and two repositioning methods (conventional and using a head immobilization shell). The mean absolute percentage difference between two corresponding scans was 6.8% (range, 1.24 to 11%) using conventional slice thickness and repositioning, 4.1% (range, 0.7 to 5.56%) using conventional slice thickness and head immobilization shells, 2.6% (range, 0.8 to 6.66%) using the conventional repositioning technique and 3-mm slice thickness, and 1.4% (range, 0.2 to 6.14%) using slice thickness of 3 mm and head immobilization shells. These mean absolute differences were significantly different (p = 0.0008). Our results indicate that the effect of repositioning errors of the order of those that can be encountered in the daily life situation of clinical trials affects significantly lesion load measurements in MS and that the combined use of thinner slices and more accurate repositioning techniques can markedly improve the reproducibility of such measurements.

Adult↗

A multicenter study on the prevalence of diabetic neuropathy in Italy. Italian Diabetic Neuropathy Committee.

OBJECTIVE: The prevalence of neuropathy, a common complication of diabetes, was determined in diabetic patients recruited from 109 outpatient diabetes clinics in Italy. RESEARCH DESIGN AND METHODS: Neuropathy was diagnosed using the Diabetic Neuropathy Index (DNI), a standardized examination developed for use in the outpatient setting. A total of 8,757 diabetic patients were studied, 51.2% men and 48.8% women, with average and median ages of 56 and 58 years, respectively. RESULTS: Of the 8,757 patients, 32.3% had neuropathy, defined as a positive score of > 2 points on the DNI. A total of 2,033 (49.6% men and 50.4% women) were administered the Diabetic Neuropathy Score (DNS), the second component of the screening program, by a neurologist. This component consists of a quantitative neurological examination and nerve conduction studies that together provide a summated score. A total of 335 patients (16.5%) were not neuropathic, and 395 (19.4%) had borderline, 453 (22.3%) mild, 592 (29.1%) moderate, and 258 (12.7%) severe neuropathy. The concordance between a positive score on the DNI and a DNS indicating neuropathy was 83.5%. The severity of neuropathy increased with both age and disease duration. Of patients with neuropathy, 64.1% had an average age between 58 and 59 years with a disease duration between 12.4 +/- 8.4 years (mild neuropathy) and 15.6 +/- 9.7 years (severe neuropathy). CONCLUSIONS: Neuropathy is a common complication of diabetes and, in this study, was present in 32.3% of all patients. An increased awareness of the high prevalence of neuropathy can lead to early therapeutic intervention and possible prevention of later neuropathic complications, such as infection and foot ulcers.

Adult↗

Copolymer-1.

Copolymer 1 (Cop-1) is a mixture of synthetic polypeptides composed of four amino acids. Cop-1 was very effective in suppression of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). Two principal mechanisms have been proposed to explain the suppressive activity of Cop-1 in EAE and in multiple sclerosis (MS): the induction of antigen-specific suppressor T cells and the interference with T-cell activation by competition with myelin antigens in binding to the major histocompatibility complex class II molecules. Clinical trials with Cop-1 have demonstrated that Cop-1 positively alters the course of relapsing-remitting multiple sclerosis (MS) by both reducing the relapse rate and slowing the progression of disability. In a 2-year multi-centre, randomized, double-blind, placebo-controlled trial of 251 patients, Cop-1 was shown to reduce relapses by an average of 29% when compared with placebo. A preliminary study on patients with relapsing-remitting MS treated with Cop-1 showed a reduced number of new enhancing lesions on MRI as well as a reduced accumulation of lesion load during Cop-1 treatment. Antibodies to copolymer-1, which are found during Cop-1 treatment, do not interfere with its clinical effects. The side effects of Cop-1 are minimal and acceptable. In vitro and in vivo animal studies have shown a very good safety profile of Cop-1 which is devoid of teratogenic or mutagenic effects. Cop-1 joins interferon beta as a good candidate for treatment of relapsing-remitting MS.

Adjuvants, Immunologic↗

Glycerol and other fermentation products of apiculate wine yeasts.

Ninety-six strains of apiculate wine yeasts were studied for their ability to produce glycerol, acetaldehyde, ethyl acetate, sulphur dioxide and hydrogen sulphide in synthetic medium. Hanseniaspora guilliermondii produced smaller quantities of glycerol, acetaldehyde and hydrogen sulphide than Kloeckera apiculata, whereas the production of ethyl acetate and sulphur dioxide was found to be similar. Strains characterized by different capacities and properties were found for both species. The existence of apiculate strains differing in secondary compound production is of technological interest, as these yeasts constitute potential flavour producers. Selected strains of apiculate yeasts might favour an enhanced flavour formation and yield desirable characteristics to the final product.

Acetaldehyde↗

Serial contrast-enhanced MR in patients with multiple sclerosis and varying levels of disability.

PURPOSE: To compare the rates of enhancement and changes in lesion burden in patients with multiple sclerosis (MS) and varying levels of disability. METHODS: Monthly enhanced MR images of the brain were obtained for 6 months from seven patients with mildly disabling relapsing-remitting MS and from seven patients with secondary progressive MS and severe disability. At entry and 1 year later, two unenhanced T2-weighted images of the brain were also obtained. RESULTS: Despite the fact that both groups had clinically active disease and had similar increases in unenhanced MR lesion load, the total number of enhancing lesions was 239 in patients with relapsing-remitting MS (42 on the baseline images, 151 new and 46 persistent during follow-up) (average number of lesions per patient per year was 68) and 21 in those with secondary progressive MS (five on the baseline images, 13 new, and three persistent during follow-up) (average number of lesions per patients per year was seven). CONCLUSION: Our data indicate that the rate of enhancement significantly decreases in the more advanced phases of MS. This is important when planning clinical trials, and suggests that mechanisms underlying lesion formation might be dissimilar in different MS patient groups.

Activities of Daily Living↗

Evoked potentials in diabetes mellitus.

Abnormalities of central afferent and efferent pathways have been revealed by evoked potential studies in diabetic patients. Central conduction time is only slightly prolonged; in afferent pathways the primary sensory neuron is more affected than in the subsequent stages, probably as an expression of a central-peripheral distal axonopathy. Central nervous system abnormalities are more frequent in patients with peripheral neuropathy, but evoked potential can be abnormal even in patients without neuropathy. Brainstem auditory evoked potential (BAEP), somatosensory evoked potentials (SEPs) and visual evoked potentials (VEPs) can be affected together, but isolated abnormalities are more frequently observed. Diffuse neuropathological changes have been found in the optic nerves, periventricular regions, brainstem and spinal cord in postmortem pathological studies. Similar changes have been found in animals with experimental diabetes. The pathophysiology of central nervous system (CNS) abnormalities is uncertain, many causes are probably active in including neural damage: chronic hyperglycemia, hypoglycemic episodes, angiopathy, blood-brain barrier dysfunction and others, still unknown.

Diabetes Mellitus↗

A high-resolution three-dimensional T1-weighted gradient echo sequence improves the detection of disease activity in multiple sclerosis.

In this study, we performed a post-contrast magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of axial slices with 5-, 3-, and 1-mm thickness in 26 patients with multiple sclerosis (MS) to investigate the disease activity going on below the resolution of conventional scans. One hundred three enhancing lesions were detected using MP RAGE reconstructed with 1-mm-thick slices, 93 using MP RAGE reconstructed with 3-mm-thick slices and 82 using MP RAGE reconstructed with 5-mm-thick slices. The detection rate using 1-mm MP RAGE was 25.6% higher compared with 5-mm MP RAGE and 12% higher compared with 3-mm MP RAGE. Using 1-mm MP RAGE, we detected five enhancing lesions in 2 of the 12 patients (16.6%) who showed no enhancing lesions on the 5-mm MP RAGE and one enhancing lesion in 1 of the 10 patients (10%) who showed no enhancing lesions on the 3-mm MP RAGE. The increased sensitivity of 1-mm MP RAGE over the other two reconstruction slice thicknesses was due to improved detection of small lesions, located mainly in cortical/subcortical areas. These data indicate that the size of enhancing lesions in MS is highly variable, and that a significant proportion of disease activity goes undetected when performing conventional scans.

Adult↗

Functional basis of memory impairment in multiple sclerosis: a[18F]FDG PET study.

Structural neuroimaging has been used to correlate lesional patterns with the cognitive profile of patients with multiple sclerosis (MS), especially for "frontal" dysfunction. However, a clear-cut anatomical explanation has yet to be found for the long-term memory deficit which is a hallmark of MS cognitive impairment. We have used PET to measure regional cerebral glucose metabolism (rCMRglc) in a group of 15 MS patients with involvement of verbal and/or spatial long-term memory. These patients were compared with 10 normal controls and 13 MS patients unimpaired on all neuropsychological tests. Relative to the controls, MS patients with memory deficits showed a significant bilateral reduction of rCMRglc in the hippocampus, cingulate gyrus, thalamus, associative occipital cortex, and cerebellum. Direct comparisons between patients with memory deficits and the group of unimpaired MS patients showed a metabolic reduction in the left thalamus and in both hippocampi. Seven of the memory-impaired patients also had neuropsychological signs of frontal dysfunction. These patients were compared with patients who had isolated memory deficit. Here we observed a further metabolic reduction in a number of brain regions including bilateral prefrontal cortex, inferior parietal cortex, and basal ganglia. Our findings indicate that hypometabolism of thalamic and deep cortical gray structures of the temporal lobe is associated with episodic memory dysfunction in MS. On the other hand, pathological performance on tests designed to assess frontal functions was associated with widespread reduction of glucose metabolism.

Adult↗

Magnetisation transfer ratios of contrast-enhancing and nonenhancing lesions in multiple sclerosis.

Magnetisation transfer (MT) is a recently introduced technique for assessing the water content of tissues in vivo and its relationship to macromolecules or membranes. It has been suggested that MT could provide indirect evidence of the characteristics of multiple sclerosis (MS) lesions (oedema, demyelination, or gliosis). Our aims were to characterise brain MS lesions and to compare the magnetisation transfer ratio (MTR) values of lesions with different patterns of contrast enhancement. In patients with MS we measured the MTR of 65 gadolinium-enhancing and 292 nonenhancing lesions. Using the equation published by Dousset et al. we studied 29 patients with clinically definite MS and 10 healthy controls. Lesions had significantly lower MT than the normal-appearing white matter of the patients or the normal white matter of healthy controls. There was no difference in the MTR of enhancing and nonenhancing lesions. Enhancement was homogeneous in 45 and ring-like in 20 lesions; MTR values were lower in the latter. These findings are presumably related to the differences in pathological features of enhancing (different amounts of proteins and inflammatory cells, oedema and demyelination) and nonenhancing (gliosis, demyelination and axonal loss) lesions.

Adult↗

A spinal cord MRI study of benign and secondary progressive multiple sclerosis.

This study was performed to achieve a better definition of the nature of the disability in multiple sclerosis (MS). Axial spinal cord magnetic resonance imaging (MRI) at C5 was obtained in 15 patients with benign MS, 17 patients with secondary progressive MS and 10 healthy controls. Patients with secondary progressive MS had smaller spinal cord cross-sectional area (P = 0.01) and transverse diameter (P = 0.006) than patients with benign MS. The degree of disability was inversely correlated with both the cross-sectional area (r = -0.6, P = 0.0018) and transverse diameter (r = -0.5, P = 0.0032) of the cord. Spinal cord atrophy was found in 7 (41%) patients with secondary progressive MS and in 2 (13%) with benign MS. These findings suggest that destructive pathology within MS lesions might play a relevant role in the development of disability in MS.

Adult↗

Magnetic resonance in monitoring the natural history of multiple sclerosis and the effects of treatment.

In this review the main contributions of magnetic resonance (MR) techniques in the monitoring of multiple sclerosis (MS) course, both natural or modified by treatments, are presented. MR measures well correlate with short-term disease evolution and therefore their use is appropriate as primary end-points in preliminary clinical trials evaluating the effects of new treatments. In contrast, the correlation between MR measures and long-term clinical evolution in clinically definite MS is less clear, thus indicating that such measures can be used at present only as a secondary end-point in large scale definitive trials. The results coming from the clinical application of newer MR techniques with higher pathological specificity are also presented and their possible future roles in monitoring treatment aimed at preventing development of disability in MS are discussed.

Brain↗

Identification of Listeria species by a semi-nested polymerase chain reaction.

Three primers derived from the lap gene were used to distinguish Listeria monocytogenes from L.innocua and other Listeria species. L. monocytogenes and L. innocua yielded a PCR product of 600 and 300 bp, respectively, whereas a typical pattern of three amplimers was observed with L. ivanovii, L. seeligeri and L. welshimeri.

Electrophoresis, Agar Gel↗

The influence of Coenzyme Q10 on total serum calcium concentration in two patients with Kearns-Sayre Syndrome and hypoparathyroidism.

Two patients with Kearns-Sayre Syndrome and hypoparathyroidism were treated with alfacalcidol (1a-OH D3) and total serum calcium concentration remained within normal range for a long period. After two months of combined therapy with Coenzyme Q10 (CoQ10), hypercalcemia was noticed and as a result, 1a-OHD3 was gradually discontinued. Normal total serum calcium concentration was obtained with CoQ10 monotherapy while the replacement of CoQ10 with placebo led to hypocalcemia. The mechanism of action of CoQ10 is difficult to explain. Since the parathormone level remained unchanged during CoQ10 or placebo therapy, we speculate that the capacity of producing an active form of vitamin D in mitochondria of proximal tubules was restored by CoQ10 therapy.

Calcium↗