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Biomedical subjects

C Fieschi

Publications and source records attributed to C Fieschi.

At least 73 records · Page 4Linked to original sources
PubMed1995

Human recombinant interferon beta in the treatment of relapsing-remitting multiple sclerosis: preliminary observations.

An open comparative, randomized trial with recombinant human interferon beta (r-hIFN-beta) involving 72 patients with clinically definite and/or laboratory-supported relapsing-remitting MS is in progress at the University 'La Sapienza' and at the S. Camillo Hospital of Rome. After a 6 month period of clinical and magnetic resonance imaging (MRI) observation (baseline findings), patients are randomly assigned to one of two treatment groups receiving 3 or 9 MIU of recombinant human IFN-beta (r-hIFN-beta) self-administered by subcutaneous injection three times a week for 6 months. All patients are examined by MRI with and without gadolinium (Gd-DTPA) every 4 weeks for the entire duration of the study (12 months). The main aim of the study is to test the hypothesis that r-hIFN-beta may halt or slow the progression of the disease by showing a significant reduction in MRI activity. This will be achieved by comparing pre and post-treatment periods. As an additional clinical end point, the exacerbation rate during these two periods will be compared. This study began in June 1993 and the final analysis of MRI data is planned for the spring of 1995.

Adjuvants, Immunologic↗
PubMed1994

Antiphospholipid antibodies and cerebral artery dissection: two frequent causes of brain ischemia in young adults.

As part of a multicenter study on ischemic stroke in the young, we report the occurrence of high antiphospholipid antibody (aPLs) levels and cerebral dissection in 75 patients. These represent the two most frequent non-thromboembolic causes of cerebral ischemia in our population. Increased aPL titres were found in nine cases (12%); cerebral artery dissection in eleven (14%). Our data stress the need to modify the classical diagnostic approach to cerebral ischemia by including hematological assessments and new neuroimaging techniques as screening tests.

Adult↗
PubMed1994

Influence of hyperglycaemia on infarct size and clinical outcome of acute ischemic stroke patients with intracranial arterial occlusion.

We investigated the effects of hyperglycaemia on infarct size of 82 acute ischaemic stroke patients with angiographically diagnosed intracranial occlusion in middle cerebral artery territory. There were 9 diabetics, 40 non-diabetic hyperglycaemics and 33 non-diabetic normoglycaemics (mean age 67 +/- 8 SD years, male/female ratio 1:1). For each patient the infarct at CT was compared to that predicted from the location of the arterial occlusion. The extent of the infarct was then classified as equal to, smaller than and larger than estimated, taking a standard anatomical template of arterial territories as reference. The results were analysed separately according to the presence or absence of a collateral blood supply (CBS) at angiography. The clinical outcome at 30 days was also evaluated. The 35 patients lacking CBS had a high frequency of equal to estimated lesions (75%), without substantial differences among the three subgroups (72% of hyperglycaemics, 82% of normoglycaemics and 67% of diabetics; Fisher's exact test not significant for any of the pairwise comparisons). On the contrary, the 47 patients with CBS exhibited an overall predominance of smaller than estimated lesions (66%) but with a very uneven distribution among hyperglycaemics, normoglycaemics and diabetics (82%, 64% and 0%, respectively; p < 0.05 at Fisher's exact test for diabetics vs hyperglycaemics). Finally, the clinical outcome was bad (death and neurological impairment) in 89% of diabetics, 72% of hyperglycaemics and 54% of normoglycaemics (p < 0.05). These results suggest that in patients with intracranial arterial occlusion associated with CBS the effects of hyperglycaemia might be beneficial in non-diabetics and harmful in diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis.

T lymphocytes from patients with multiple sclerosis (MS) recognize multiple myelin basic protein (MBP) epitopes. This situation complicates the design of specific immunotherapies. We investigated to which extent the T cell response to MBP is heterogeneous in single subjects in terms of preferentially recognized regions of the molecule, major histocompatibility complex (MHC) restriction, and stability over time. From each of nine patients with MS, a minimum of six MBP-specific T lymphocyte lines (TLL) were assayed for the proliferative response to a panel of overlapping peptides, encompassing the whole MBP. Predominant T cell recognitions of distinct MBP regions were present in three patients, all HLA-DR2+, independently of the clinical features of their disease. T cell reactivity was preferentially directed to residues 16-38 in one patient. In this case the response was also stable over time, during different phases of the disease. Predominant reactivity to residues 86-99 was detected in the two other DR2+ patients. In each of the patients with other HLA-DR haplotypes (DR2-), as well as in three DR2+ non-MS donors, the T cell response to MBP appeared to be considerably more heterogeneous. The HLA restriction element varied among TLL recognizing the same MBP region, even when raised from the same individual. The genomic HLA typing, performed on the DRB1 and DRB5 genes in the DR2+ subjects, showed no obvious correspondence between preferential responses to regions of MBP and HLA-DR2 subtypes. In this context, a simple, new method for the genomic typing of the HLA-DRB1 gene in individuals with the HLA-DR2 serological specificity is also described. We conclude that predominant and stable T cell responses to a single MBP region can be detected in some patients with MS. In these individuals, the MHC restriction of the T cell recognition of predominant regions appears to be variable. Polymorphisms of the HLA-DR2 gene products alone do not account for the selection of the dominant MBP T cell epitope.

Adolescent↗
PubMed1993

Target epitopes of myelin basic protein specific T cell lines in multiple sclerosis.

A highly efficient new method for the generation of antigen specific T cell lines (TCL) is now available. By this method we established 134 myelin basic protein (MBP) TCL from the peripheral blood of 9 patients with definite multiple sclerosis (n = 69) and 8 healthy donors (n = 65). The yield of MBP reactive TCL in the two groups was comparable. So far 22 MBP specific TCL from 7 patients and 24 from 7 healthy individuals have been tested for their proliferative response to a panel of four synthetic peptides representing MBP residues 7-26, 80-99, 139-153 and 148-162. Although the peptide sequences did not encompass the whole MBP, the pattern of reactivity to these peptides in patients and controls seems to be similar. Further, when multiple TCL from the same donor were analysed, no dominant recognition emerged.

Adult↗
PubMed1993

Anatomical and functional correlates of cognitive deficit in multiple sclerosis.

This brief article reviews the present state of knowledge concerning the relationship between structural and functional cerebral abnormalities and the cognitive deficits associated with multiple sclerosis. Currently available neuroimaging techniques have substantially contributed to a better understanding of the latter, suggesting that cortical-subcortical disconnection is the most likely cause of the cognitive disturbance. Longitudinal studies are needed to determine the natural history of the cognitive deficit and its relationship to the cerebral changes detected by neuroimaging techniques.

Cognition Disorders↗
PubMed1993

Focal cerebral ischemia in young adults: a collaborative case-control study. The National Research Council Study Group.

Because there is uncertainty about the role of atherogenic and nonatherogenic risk factors for cerebral ischemia in the young, we carried out a multicenter, hospital-based, case-control study. 333 patients (15-44 years) with focal cerebral ischemia (transient ischemic attack or stroke within 8 weeks of admission) were eligible. 25 patients were excluded, according to the protocol. 308 cases were matched by age and gender to one hospital and one population control. Independent risk was shown by logistic conditional regression for migraine with aura [odds ratio (OR) = 14.8], smoking (OR = 3.7), alcohol (OR = 2.8), serum triglycerides (OR = 1.6), arrhythmias (OR = 9.5), mitral stenosis (OR = 56), coronary heart disease (OR = 4.3) and carotid stenosis or occlusion (OR = 41). Serum HDL-cholesterol had a relative protective effect (OR = 0.8). These data confirm the role of atherosclerosis and cardiac diseases as well as migraine with aura and alcohol consumption in the pathophysiology of cerebral ischemia in the young. More thorough prevention programs may contribute to earlier detection and control of all of these risk factors, but further investigations in patients with as yet unidentified risk factors are warranted because the above-mentioned factors do not account for the total risk of ischemic stroke in the young.

Adolescent↗
PubMed1993

A prospective study of cerebral ischemia in the young. Analysis of pathogenic determinants. The National Research Council Study Group.

BACKGROUND AND PURPOSE: The etiology of stroke in the young is different from that in older patients and remains unknown in almost one third of the cases. To gain further insight into both pathogenic and etiologic determinants, we prospectively studied a large number of consecutive young adults with focal cerebral ischemia. METHODS: Three hundred thirty-three patients aged 15-44 years with transient ischemic attack or ischemic stroke within the 8 weeks before hospital admission were recruited and investigated by using a standardized protocol of clinical evaluation, blood tests, electrocardiography, echocardiography, chest roentgenography, and brain computed tomography. Presumed etiology was diagnosed by prospectively applied criteria. RESULTS: Women predominated (61%) among patients under 35 years of age, mainly due to the frequency of cerebral ischemia related to oral contraceptive use, while men outnumbered women (60%) among patients over that age because of a higher prevalence of atherothrombotic disease. Potential cerebral embolism of cardiac origin was the presumed cause of stroke in 23.7%, but conventional sources of emboli were found only in 7.5% of cases. There was a low prevalence of atrial fibrillation among young patients with cerebral ischemia. Mitral valve prolapse was found in 8.4%, as expected, predominantly (71.4%) among the younger patients. The prevalence of stroke over transient ischemic attack was proportional to the likelihood of cardiac embolism. Acute alcohol intoxication was considered a precipitating factor in only three patients. The percentages of cerebral ischemia attributed to arterial dissection (0.3%), oral contraceptive use in women (8.1%), migraine (1.2%), and other associated medical diseases (1.5%) were lower than reported in recent clinical series. CONCLUSIONS: Two different groups of pathogenic determinants predominate in younger women and in older men, supporting public health measures aimed at strict medical control of the recognized cerebrovascular risk factors.

Adolescent↗
PubMed1993

Metabolic mapping of the pharmacological and toxicological effects of dopaminergic drugs in experimental animals.

Functional consequences of pharmacological and toxicological manipulations of the dopaminergic systems were evaluated by means of the 2-[14C]deoxyglucose (DG) method for measuring local rates of cerebral glucose utilization. Administration of dopamine agonist drugs modifies glucose metabolism in selected brain areas. Several factors, such as the compound used, the dose, length, and modality of the treatment, and the interval of time between the end of the treatment and the measurement of glucose utilization, contribute to define the topography and intensity of the changes. The differences refer to distinct activation of subtypes of dopamine receptors, to secondary involvement of other neurotransmitter receptor systems, and to modification of the receptor sensitivity occurring during the treatment. Other variables that interfere with the motivated behavior induced by psychostimulants may also affect the metabolic pattern. A few changes in glucose utilization are, however, common to most dopamine agonist drugs. High doses, which induce stereotypic behavior, produce metabolic changes in the extrapyramidal system. Low doses of psychostimulants, which elicit locomotion and exploratory behavior and produce reinforcement, increase glucose metabolism in the limbic system, particularly in the nucleus accumbens. Metabolic mapping in monkeys bearing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lesions of the dopaminergic areas in the brainstem contributed to define the key role of the striatopallidal pathway in the production and maintenance of the motor abnormalities that characterize parkinsonism. Metabolic patterns associated with unilateral 6-hydroxydopamine lesion of the nigrostriatal neurons in the rat are modified by dopamine agonist drugs. Specific changes are produced by selective D1 or D2 agonists. In rats bearing unilateral 6-hydroxydopamine lesion, the DG method also revealed functional effects produced by the interaction between D1 and N-methyl-D-aspartate receptors.

Animals↗
PubMed1992

Tumor necrosis factor-alpha and interferon-gamma synthesis by cerebrospinal fluid-derived T cell clones in multiple sclerosis.

T cell clones derived from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) were analysed for their capacity to produce interleukin 2 (IL-2), interleukin 4 (IL-4), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). They were also compared with liver-infiltrating T cell clones from patients with chronic active hepatitis. All the CSF T clones (both CD4+ and CD8+) produced large amounts of IFN-gamma and particularly of TNF-alpha, that was synthesized in a significantly larger amount than compared clones. Moreover, they were capable of secreting IL-2, but not IL-4. From our results, we conclude that first, the CSF CD4+ T clones could constitute a subset with functional properties similar to the T helper 1 (Th1)/inflammatory cell subset of the mouse; and second, the large amounts of TNF produced by CSF T cell clones strongly suggests a significant role for this cytokine as well as of IFN-gamma in MS immunopathogenesis.

Adult↗
PubMed1992

Motor stimulation response by technetium-99m hexamethylpropylene amine oxime split-dose method and single photon emission tomography.

We applied the technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) split-dose method in order to evaluate the feasibility of assessing cerebral blood flow (CBF) changes with single photon emission tomography (SPET) during a motor activation task. Eleven normal subjects were studied using the Tomomatic 564 (Medimatic, DK). Five subjects were studied twice at rest and 6 subjects at rest and during a motor task performance (finger opposition movements). A total of 28 mCi of 99mTc-HMPAO was injected in 2 doses with a 1:3 ratio. The first scan was obtained after injection of 7 mCi at rest in all subjects. The second scan was obtained a few minutes later, after injection of the remaining dose (21 mCi), under similar resting conditions or during a motor task performance. The mean brain uptake was proportional to the amount of tracer injected and to the acquisition time for both the first scan (5263 +/- 1266 counts x mCi x min) and the second (5034.4 +/- 966 counts x mCi x min). The grey/white matter ratio was 1.67 +/- 0.019 and 1.67 +/- 0.097 for the two scans, respectively. A three-way analysis of variance (ANOVA) for repeated measure showed no significant effects of side, slice and region of interest (ROI) on the CBF in the 5 subjects studied twice at rest, and the mean regional CBF change was -0.2% +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1992

Does hyperglycaemia play a role on the outcome of acute ischaemic stroke patients?

A consecutive series of 327 patients (188 males, 139 females; mean age 68.4, SEM 1.33) were hospitalized within 12 h of the onset of their first-ever hemispheric infarct. Three groups of patients were identified: diabetics (n = 70), non-diabetic hyperglycaemics (n = 93) and normoglycaemics (n = 164). Case-fatality ratios at 30 days after stroke were 38.6%, 22.6% and 9.2% (P less than 0.001) respectively, whereas the causes of death and functional outcome of survivors were not significantly different between the groups. Mean admission serum glucose levels (SGLs) of decreased, impaired/unchanged and improved patients within each one of the three groups, were also not significantly different as opposed to their mean Canadian Neurological Scale (CNS) scores at entry (P less than 0.01). Among patients with less severe initial neurological deficit (i.e., CNS score greater than or equal to 7.0), 82.6% of non-diabetic hyperglycaemic subjects fared well, in comparison with 56.5% of diabetic and 70.1% of normoglycaemic individuals. The size of the infarcted areas at the second CT correlated with mean CNS scores (P less than 0.01) but not with mean SGLs on admission. The site of the ischaemic areas did not correlate with mean SGLs at entry. Therefore the influence of initial SGLs on the clinical course of the present series of patients is questionable or, alternatively, varied probably according to the pattern of residual cerebral blood flow after arterial occlusion.

Aged↗