Absolute quantification of brain metabolites by proton magnetic resonance spectroscopy in normal-appearing white matter of multiple sclerosis patients.

The aim of this research was to obtain an absolute quantification of the N-acetyl-aspartate, choline, creatine and phosphocreatine levels in normal-appearing white matter by means of 1H magnetic resonance spectroscopy in a group of multiple sclerosis patients (27 with the relapsing-remitting form and 13 with the secondary progressive form). These values were compared with those of a group of 12 age-matched healthy control subjects. A significant decrease in the N-acetyl-aspartate concentration was found in normal-appearing white matter of frontal and parietal brain areas in multiple sclerosis patients compared with the same areas in control subjects. This reduction was more evident in progressive patients. The decrease in the N-acetyl-aspartate concentration in normal-appearing white matter significantly correlated with the Expanded Disability Status and the lesional load. No significant change was found in the concentration of creatine or choline. This finding concurs with previous evidence of heterogeneity in the multiple sclerosis pathological process which is not confined to the lesions and involves not only myelin, but also axons, even in white matter which appears normal on MRI.

Cytokine secretion and nitric oxide production by mononuclear cells of patients with multiple sclerosis.

Several experimental findings suggest a potential role of excessive nitric oxide (NO) production by macrophages, microglia and astrocytes in the pathogenesis of demyelinating lesions in MS. We assessed the production of nitrites by peripheral blood mononuclear cells (PBMCs) of 15 MS patients (10 F and 5 M) with the R-R form (EDSS: 1-3.0) and in 15 age-matched control subjects. 9 out of the 15 MS patients showed active lesions in MRI at the time of examination. 7 patients were also monitored at the onset, during and following a clinical relapse. Secretion of cytokines by PBMCs was assessed at the basal time and after 24 h of incubation with lipopolysaccharide (LPS). The production of nitrites in the supernatants of PBMCs stimulated and not stimulated with lipopolysaccharide was evaluated. The secretion of IL1 beta, IFN-gamma, TNF-alpha, IL-6 IL-10 and TGF-beta by PBMCs was detected using ELISA methods. The production of NO, both basal and stimulated, was significantly higher in the patients with active lesions than in those without active lesions (p < 0.01). No significant difference was evident between the basal and LPS-stimulated production of NO between control subjects and MS patients without active lesions. During relapses there was a significant increase in NO production by PBMCs compared to the clinical stable stage of the disease (p < 0.0001). This increase was significantly greater in the early stage of relapse than in the late stage (p < 0.04). A decline of NO levels was observed during recovery. Steroid treatment induced a significant decrease in the PBMC NO production of MS patients during exacerbations (p < 0.01). The levels of IL-1 beta, IFN-gamma and TNF-alpha are significantly higher in the supernatants of the PBMCs which produced greater amounts of NO (p < 0.02, p < 0.03, p < 0.01, respectively). On the other hand, NO levels were negatively related to IL-10 and TGF-beta production (R = -75, p < 0.0001 and R = -0.79, p < 0.0001, respectively). The increase production of NO by peripheral blood mononuclear cells demonstrated in our study to be associated with increased production of proinflammatory cytokines could therefore be considered to be a marker of mononuclear cell activation in the peripheral blood of MS patients and, indirectly, of disease activity. Its increased secretion during T cell and monocyte homing in the CNF could contribute to the damage to the blood-brain barrier and the subsequent cytokine-mediated cytotoxic effect to myelin and oligodendrocytes in the white matter of MS patients.

[Ventricular hypoplasia in congenital heart diseases]. / Le ipoplasie ventricolari nelle cardiopatie congenite.

Twenty-seven cases of autopsy showing hypoplasia of one of the ventricular cavities, prevalently the left, were selected from a series of 103 congenital cardiopathies (1979-1990). In 9 cases ventricular hypoplasia formed part of complex malformative syndromes with a well-known physiognomy: a further 18 cases showed a complete (9 cases) or incomplete (9 cases) hypoplastic heart syndrome. Subjects were prevalently female and the presence of other malformations indicating a genetic dysfunction was less evident than in other cardiopathies. The different pathogenetic hypotheses are discussed in the light of macro- and microscopic morphological factors, of which the most plausible is that involving an anomalous position or orientation of the musculo-membranous folds which give rise to the septation system of the various metamers of the cardiac tube.