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Biomedical subjects

G Comi

Publications and source records attributed to G Comi.

At least 325 records · Page 18Linked to original sources
PubMed1995

Acute transverse myelopathy: spinal and cranial MR study with clinical follow-up.

PURPOSE: To evaluate the contribution of MR in determining the cause of acute transverse myelopathy, to determine the frequency and types of the intracranial lesions detectable on MR at the onset of the disease, and to monitor clinical and MR evolution of the disease. METHODS: Spinal and cranial MR images were obtained for 30 patients with acute transverse myelopathy. Gadopentetate dimeglumine was administered in 10 patients. Mean follow-up time was 18 months. RESULTS: Spinal cord MR findings were abnormal in 14 of 30 patients. The abnormal MR can be divided into group A, in which one segment was involved (8 patients), and group B, in which more than one segment was involved (6 patients). In both groups there were 2 patients with enhancing lesions. Enhancement was less homogeneous in the group B patients. Enhancement did not change with increased length of lesion. At follow-up, the diagnostic categories of the patients were multiple sclerosis (8 patients), encephalomyelitis (1 patient), viral myelitis (3 patients), and myelopathy of unknown cause (18 patients). After the episode of acute transverse myelopathy, in 4 of 8 patients in group A and in 4 of 5 patients with normal spinal MR but abnormal brain MR findings clinical signs of multiple sclerosis developed. In no patients in group B did multiple sclerosis develop. The final diagnoses for the 4 patients with gadolinium-enhancing spinal lesions were myelopathy of unknown cause (2 patients), multiple sclerosis (1 patient), and viral myelitis (1 patient). CONCLUSION: MR contributed to establishing the diagnosis in 40% of our cases.

Acute Disease↗
PubMed1995

Polymerase chain reaction assay for detection of Campylobacter coli and Campylobacter jejuni in poultry meat.

Primers of 16S rRNA and flaA genes were used to optimise a PCR technique for detecting thermotolerant campylobacters in poultry meat. Different methods for crude DNA extraction were also evaluated. The use of flaA primers and extraction of nucleic acid by boiling and proteinase K gave good results in the detection of Campylobacter either in artificially or naturally contaminated foodstuffs. The lowest sensitivity limit for the PCR reaction was 10(1)-10(2) thermophilic Campylobacter cells either in pure cultures or in artificially and naturally contaminated poultry skins, corresponding to a concentration of 10(2)-10(3) Campylobacter/ml or g product. The PCR method we devised had a high sensitivity and specificity. It appears to give better results than conventional methods and is very easy and fast, requiring only eight hours to detect thermotolerant Campylobacter from poultry meat. In contrast, conventional methods require almost 4 days.

Animals↗
PubMed1995

Early treatment of multiple sclerosis with Rebif (recombinant human interferon beta): design of the study.

Two recent properly controlled trials performed in patients with relapsing-remitting MS have demonstrated that interferon beta substantially improves the evolution of the disease. The results of the Optic Neuritis Treatment Trials suggest that early treatment of patients with isolated optic neuritis may delay the conversion to clinically definite MS (CDMS). Moreover, clinical trials in MS and in immune-mediated diseases indicate that better results are obtained in patients in the early phases of the disease. We present the design of a multicentre, randomized, double-blind, placebo-controlled study of recombinant interferon beta (Rebif-Serono) in patients with a first attack suggestive of MS. The primary objective of the study is to investigate the efficacy of Rebif, administered subcutaneously at the dose of 8 million international units (MIU) once a week for 2 years, on the risk of developing CDMS.

Adjuvants, Immunologic↗
PubMed1994

Gamma interferon activates a previously undescribed Ca2+ influx in T lymphocytes from patients with multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. The etiology of the disease is still unknown. Activated T lymphocytes are considered essential in mediating the inflammatory process leading to demyelination in MS. They operate through a complex network of cytokines among which gamma interferon (gamma-IFN) plays a key role. Here we report that exposure to gamma-IFN of T lymphocytes from patients with MS activates, by a protein kinase C-mediated pathway, a previously undescribed gamma-IFN-activated Ca2+ influx, functionally coupled to the gamma-IFN receptor. The influx mainly expressed by CD4+ T lymphocytes, was found in 12 of 15 (80%) patients with clinically active MS and in 14 of 30 (46%) patients with stable MS. The influx was found in only 3 of 24 (12%) control patients and in none of the 15 healthy subjects studied. Our results document the appearance in MS lymphocytes of a gamma-IFN-activated, protein kinase C-dependent, Ca2+ influx that might be due to the expression of a new cation-specific plasmalemma channel. This finding suggests that at least part of gamma-IFN's contribution to the pathogenesis of MS is exerted through a Ca(2+)-dependent regulation of T lymphocyte activity.

Adult↗
PubMed1994

Autoantibodies to glutamic acid decarboxylase in palatal myoclonus and epilepsy.

We report the presence of serum autoantibodies directed against glutamic acid decarboxylase in a patient with epilepsy and palatal myoclonus not associated with brain lesions. Glutamic acid decarboxylase antibody reactivity was dependent on the presence of carboxy-terminal amino acids, similar to that reported in patients with stiff-man syndrome. Marked reduction in the frequency of epileptic attacks and improvement in palatal myoclonus occurred when benzodiazepine was administered and phenytoin was gradually tapered. Testing for anti-glutamic acid decarboxylase antibodies may be indicated in patients with palatal myoclonus and with convulsive disorders refractory to therapy.

Adult↗
PubMed1994

Nocturnal sleep study in multiple sclerosis: correlations with clinical and brain magnetic resonance imaging findings.

It has been suggested that sleep disturbances in multiple sclerosis (MS) may be related to periodic leg movements (PLM) during sleep, but to date polysomnographic studies were conducted only on small and unselected patient groups. Aim of this study was to evaluate 8-hour polysomnography in MS patients and to correlate sleep results with clinical and brain magnetic resonance imaging (MRI) data. Twenty-five clinically definite MS patients, without mood disorders and drug-free, entered the study. The patients were compared to 25 age- and sex-matched subjects. MS patients had significantly reduced sleep efficiency and experienced more awakenings during sleep. No difference was found in sleep architecture parameters between MS patients and controls. PLM was found in 9 patients (36%) and 2 controls (8%; p = 0.02). Of the six patients who complained of insomnia two had PLM and 2 others presented with PLM and central sleep apnea. In patients with PLM greater MRI lesion loads were detected in the infratentorial regions, particularly in cerebellum and brainstem. Larger studies in neurological diseases that produce focal lesions in these brain areas could provide useful information on the PLM pathogenesis.

Adult↗
PubMed1994

Multiple deletions of mitochondrial DNA in sporadic and atypical cases of encephalomyopathy.

Multiple deletions of mitochondrial DNA (mtDNA) were first identified in patients with mitochondrial encephalomyopathy with a clear mendelian inheritance. We found this genetic alteration in four atypical and sporadic cases of mitochondrial encephalomyopathy, characterized by RRF and partial COX deficiency. One patient was affected by essential hyperCPKemia, 1 by subacute onset flaccid tetraplegia and 2 by parkinsonism. Southern blot and PCR revealed mtDNA multiple deletions in muscle tissue of these patients. These findings indicate that these alterations are not confined to the families with mendelian transmission, but can be present in sporadic cases with heterogeneous phenotypic features.

Aged↗
PubMed1994

Chronic progressive external ophthalmoplegia: a correlative study of quantitative molecular data and histochemical and biochemical profile.

We studied muscle biopsies of 5 patients with Kearns-Sayre syndrome and 3 patients with chronic progressive external ophthalmoplegia all with the common deletion. Steady state levels of normal and deleted mitochondrial DNA (mtDNA) measured in each patient by quantitative PCR were correlated with histochemical and biochemical features. We found that (1) normal mtDNA levels were higher in many patients than in controls; (2) as levels of deleted mtDNA increased, so did levels of normal mtDNA; (3) cytochrome c oxidase (COX) activity and the percentage of COX negative fibers were both related to the levels of deleted mtDNA; and (4) as percentage of ragged red fibers increased, so did levels of total, deleted and normal mtDNA. The quantity of deleted mtDNA plays a key role in determining the severity of COX deficiency, which is responsible for the overaccumulation of mitochondria in muscle.

Adolescent↗
PubMed1994

Absence of central nervous system pathology in severe combined immunodeficiency mice intraperitoneally injected with peripheral blood lymphocytes from multiple sclerosis patients.

In order to reproduce some of the pathological features of multiple sclerosis (MS) we transplanted peripheral blood lymphocytes (PBLs) from seven patients with MS into the peritoneal cavity of 28 severe combined immunodeficiency (MS-SCID) mice. Seven SCID mice were also transplanted with PBLs from two healthy subjects (hu-SCID). Animals were sacrificed between 2 and 8 weeks after transplantation (a.t.). Polymerase chain reaction (PCR) using primers able to amplify the HLA-DQ alpha region showed presence of human cells in neural tissues of MS-SCID mice. Immunocytochemical analysis revealed the scattered appearance of human lymphocytes (mostly CD45RO+ T cells) in the meningeal space and choroid plexuses of MS-SCID brains. However, human lymphocytes were similarly found in brains of hu-SCID mice. Both groups of mice never showed signs or symptoms of neurological impairment. Our results indicate that the simple transplantation of lymphocytes from MS patients into SCID mice is not likely to produce an MS-like pathology.

Animals↗
PubMed1994

Clinical and neurophysiological assessment of immunoglobulin therapy in five patients with multifocal motor neuropathy.

High dose intravenous immunoglobulin (IVIg) is an effective treatment for demyelinating neuropathies. IVIg was given to five patients with multifocal motor neuropathy, a motor neuropathy showing a clinical syndrome of asymmetrical weakness and amyotrophy, electrophysiological evidence of motor conduction block and, in many cases, high titres of serum anti-GM1 antibodies. Muscle strength was evaluated by a conventional score before and after each IVIg course. In all patients there was relevant improvement on muscle strength after each immunoglobulin course, but in most cases the clinical benefits partially declined after three to eight weeks. At the eight month follow up, however, the pretreatment examination showed a significant improvement compared with the initial evaluation. The effects of each IVIg course were still present after a number of courses. Electrophysiological study revealed a decrease in conduction block in one or more nerves in all patients. However, conduction block was unchanged or increased in other sites. IVIg treatment did not affect anti-GM1 antibody titres.

Adult↗
PubMed1994

Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating neuropathy not responsive to other treatments.

Nine patients with chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) were treated with intravenous immunoglobulin. All patients had been previously treated with prednisone and/or plasma exchange without effect. Objective improvement in clinical condition occurred in six patients. One patient became refractory after two treatment courses, two patients had no response. The results indicate that intravenous immunoglobulin has beneficial effects in a high percentage of patients with CIDP who are unresponsive to other treatments.

Adult↗
PubMed1994

Influence of clinical variables on neuropsychological performance in multiple sclerosis.

The effects of age, educational level, duration and course of the disease, physical disability and mood status on several cognitive functions (short- and long-term memory, frontal functions, attention, language and visuospatial skills) have been evaluated in 42 multiple sclerosis (MS) patients. The Hamilton Depression Rating Scale (HDRS) scores and a secondary progressive disease course significantly influenced neuropsychological performance. Factorial analysis revealed that indexes of (1) frontal function impairment, (2) long-term verbal memory and language function impairment, and (3) visuospatial short- and long-term memory and visuoperceptive function impairment accounted for 85% of the variance in neuropsychological performance. Only the first factor was significantly related to the presence of depressive symptomatology, as assessed by the HDRS. These results indicate that both the course of the disease and the presence of affective disorders must be taken into account when evaluating the natural history of cognitive impairment in MS and suggest that depressive symptomatology and cognitive dysfunction in MS are related to the involvement of at least partially overlapping anatomofunctional circuits.

Adult↗
PubMed1994

Electrophysiologic studies in tarsal tunnel syndrome. Diagnostic reliability of motor distal latency, mixed nerve and sensory nerve conduction studies.

The tarsal tunnel syndrome (TTS) is an entrapment of the posterior tibial nerve at the ankle, which, like carpal tunnel syndrome, improves with surgery but needs an instrumental diagnosis to exclude other diseases. This study was performed to evaluate the diagnostic value of nerve conduction tests proposed for the diagnosis of TTS. Of the 13 patients who were investigated 12 had secondary unilateral and 1 idiopathic bilateral TTS. One or more neurophysiologic parameters were abnormal in all cases. The diagnostic value of each neurophysiologic parameter was calculated by comparing conduction on the affected side with conduction on the healthy side of each patient with TTS. The accuracies of the sensory nerve action potential and mixed nerve action potential, both after stimulation of the plantar nerves, were almost the same, with sensory nerve action potentials more sensitive and less specific and mixed nerve action potentials less sensitive and more specific. Because from the clinical point of view we must be more afraid of false-positive results, the mixed nerve action potential is recommended for presurgical diagnosis of TTS. Coexistence of mixed nerve and sensory nerve action potential abnormalities, especially if asymmetric, are highly indicative of TTS.

Action Potentials↗
PubMed1993

6-[18F]fluoro-L-dihydroxyphenylalanine metabolism and positron emission tomography after catechol-O-methyltransferase inhibition in normal and hemiparkinsonian monkeys.

Increased and sustained central delivery of L-dihydroxyphenylalanine (L-DOPA) is a desirable therapeutic strategy in Parkinson's disease. We investigated the effects of peripheral catechol-O-methyltransferase (COMT) inhibition, by the non-toxic drug nitecapone on the metabolism of 6-[18F]fluoro-L-dihydroxyphenylalanine (6FD) and on its positron emission tomography (PET) imaging in non-human primates. Nitecapone produced a dose-dependent inhibition in the formation of 3-O-methyl-6-[18F]fluorodihydroxyphenylalanine (OMFD). This inhibition of OMFD formation was attended by increased production of other metabolites, in particular 6-[18F]fluorodopamine (6FDA), 6-[18F]fluorodihydroxyphenylacetic acid (FDOPAC), 6-[18F]fluorohomovanillic acid (FHVA) and [18F]-sulfated conjugates (FSC). Although nitecapone had no effect on plasma 6FD pharmacokinetics, high-dose nitecapone increased contrast of cerebral 18F uptake and retention between regions with high (striatum) versus sparse (parieto-occipital lobes) dopaminergic innervation. 18F uptake contrast was also improved between structures known to possess an intermediate dopaminergic innervation, including the upper brainstem, frontal and temporal lobes, versus sparsely innervated regions. This increased contrast was secondary to decreased activity in sparsely innervated structures and not to increased activity in highly innervated structures. Contrast was correlated inversely with the plasma OMFD/6FD concentration ratio, OMFD being the main 6FD metabolite which can cross the blood brain barrier. We conclude that nitecapone is an effective inhibitor of COMT in non-human primates. This inhibition results in increased 6FD flux through other catabolic pathways. Because of decreased OMFD formation, however, COMT inhibition improves the specificity of 6FD-PET and facilitates in-vivo detection of a wide range of dopaminergic innervation densities in cerebral structures.

Animals↗
PubMed1993

Heterogeneity of autoantibodies in stiff-man syndrome.

Stiff-man syndrome is a rare neurological disorder characterized by skeletal muscle rigidity and spasms in which detection of circulating anti-glutamic acid decarboxylase antibodies has suggested an autoimmune pathogenesis. To further define the role of autoimmunity in the pathogenesis, we studied anti-glutamic acid decarboxylase antibodies, as well as organ- and non-organ-specific autoantibodies in 13 patients with stiff-man syndrome and 127 patients with other neurological disorders. Thyrogastric antibodies were more frequent in patients with stiff-man syndrome (46%) than in those with other neurological disorders (12%) (p < 0.05). Non-organ-specific antibodies were found at a similar frequency in the patients with stiff-man syndrome (61%) and those with other neurological disorders (65%). Islet-cell autoantibodies and anti-glutamic acid decarboxylase antibodies were more common in stiff-man syndrome patients (38% and 31%) compared to the patients with other neurological disorders (6% and 3%, respectively; p < 0.001). With the exception of 1 patient in the other neurological disorders group, anti-glutamic acid decarboxylase antibodies were always associated with islet-cell autoantibodies. Four patients with stiff-man syndrome had an associated solid tumor: 3 of them had antibodies recognizing a 125/130-kd protein and not glutamic acid decarboxylase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Presence of T-cell subset abnormalities in newly diagnosed cases of multiple sclerosis and relationship with short-term clinical activity.

Abnormalities of T-cell subsets in patients with multiple sclerosis are well known; in order to assess whether immunological abnormalities are relevant in the pathogenesis of the disease after its clinical onset, peripheral blood lymphocyte subsets (CD3+, CD4+, CD4(+)-CD45RA+, CD4+CD45RA-, CD8+, CD8+CD57+, CD57+, CD25+) were analysed serially in 25 patients at the first clinical episode suggestive of inflammatory demyelinating disease and in an equal number of age- and sex-matched controls. During the follow-up period (12-18 months, mean 14) 6 of 25 patients presented new relapses: in this subgroup of patients, significant changes in CD4+ ratio (% CD4+CD45RA-/%CD4+CD45RA+) were detected in comparison both with healthy controls and with clinically stable patients. Patients clinically stable at follow-up did not display immunological abnormalities, regardless of the presence or absence of cerebrospinal fluid and/or magnetic resonance imaging alterations consistent with multiple sclerosis. These findings suggest a possible prognostic role of early T-cell subset imbalance in multiple sclerosis.

Adolescent↗