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Biomedical subjects

A Federico

Publications and source records attributed to A Federico.

At least 73 records · Page 4Linked to original sources
PubMed2002

Open Facilities for Training in European Neurology (OFTEN): a European Board of Neurology initiative.

The European Board of Neurology has established Open Facilities for Training in European Neurology (OFTEN) by creating a databank of excellent or good neurological departments from 14 European countries willing to receive trainees from abroad (http://www.uems.be/neuro.htm). Further expansion of this databank with an increased number of participating departments and countries is planned. The databank should make it easier both to find a relevant department for training abroad and to obtain funding from various sources. No financial support is available in the program itself. The ultimate aim of this cross-European training is to improve neurological skill, knowledge and attitude. It will also promote European co-operation and harmonization in quality of care.

Databases, Factual↗
PubMed2002

Functional reorganization of motor cortex increases with greater axonal injury from CADASIL.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-artery disease that clinically involves only the brain. Particularly early in the disease, patients can show substantial or complete recovery after individual strokes. Cortical functional reorganization may contribute to limiting disability with such ischemic injury. We sought to test whether the extent of any functional changes in the motor cortex increases with greater brain axonal injury from CADASIL. METHODS: Functional MRI (fMRI) was used to characterize cortical activation during a simple hand-tapping task. Disease-associated pathology in subcortical white matter was assessed with the use of conventional fluid-attenuated inversion recovery (FLAIR) MRI and MR spectroscopic imaging for measurement of N-acetyl aspartate decreases, a relatively specific measure of axonal injury. RESULTS: There was evidence for variable but substantial hyperintense white matter signal in all of the patients with FLAIR imaging. With the use of fMRI, the brain regions activated during motor tasks were similar for the 9 CADASIL patients and 7 controls, except that most (6 of 9) patients showed primary motor cortex activation both ipsilateral and contralateral to the hand moved, a finding in only 1 of 7 healthy controls. Ipsilateral motor cortex activation increased (r=-0.77, P<0.05) and motor cortex activation lateralization index decreased (r=0.68, P<0.02) with greater white matter injury (as assessed from decreases in the relative N-acetyl aspartate concentration) in a region of interest including descending motor fibers of the corticospinal pathway. CONCLUSIONS: The extent of functional reorganization of motor cortex increases with increasing axonal injury, consistent with an adaptive role for these changes. Increased functional recruitment of cortex ipsilateral to the limb moved therefore may contribute to limiting motor impairment from the subcortical injury of CADASIL.

Adaptation, Physiological↗
PubMed2002

Nemaline myopathy: description of an adult onset case.

Nemaline myopathy is a rare congenital muscle disease, with neonatal or adult onset. We report clinical and ultrastructural study of a 73-year-old woman whose symptoms manifested at age 40 years with proximal muscle weakness, nocturnal cramps, muscle pain and walking impairment. Muscle biopsy showed rods and other typical findings suggesting nemaline myopathy. This myopathy should be taken into account in the differential diagnosis of adult onset myopathies. Only ultrastructural examination allows an exact diagnosis.

Aged↗
PubMed2001

Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in five patients. An electrophysiological study.

We report the electrophysiological follow-up of five cerebrotendinous xanthomatosis patients treated for 11 years with chenodeoxycholic acid (CDCA). Nerve conduction velocity (NCV) was reduced in three cases. P100 latency of visual evoked potentials was delayed in four cases, interpeaks I-III and I-V of brainstem auditory evoked potentials (BAEPs) was increased in two and interpeak N13-20 of upper limb somatosensory evoked potentials (SEPs) was slowed in one. After 4 months of therapy with CDCA, NCV was normal and did not show any significant change during the 11 years of observation. Central motor conduction time of motor evoked potentials (MEPs) and N24-P40 interpeak latency of lower limb SEPs were increased in five and four cases, respectively, in spite of 2/3-year treatment with CDCA. Improvement of evoked potentials, especially of MEPs and SEPs, was slower and continued over the whole 11-year period. The size of xanthomas slightly decreased in some patients during treatment and the clinical manifestations stabilized, avoiding progressive worsening, but there was no significant improvement in neurological deficit. Two sisters of patients who never took CDCA showed progressive worsening of clinical manifestations, upper limb SEPs and BAEPs.

Adult↗
PubMed2001

Correlates of MS disability assessed in vivo using aggregates of MR quantities.

OBJECTIVES: To assess the magnitude of the correlations between disability and composite MRI scores in patients with MS. METHODS: T2- and T1-weighted MRI, magnetization transfer imaging, diffusion tensor imaging, and MRS imaging scans of the brain from 23 patients with MS were obtained. T2 lesion volume, T1 lesion volume, brain magnetization transfer ratio, average brain diffusivity (D), and brain N-acetylaspartate/creatine ratio were measured. RESULTS: The correlations between the Expanded Disability Status Scale (EDSS) score and each of the MR quantities taken in isolation were not significant, with the exception of the correlation between EDSS and the NAA/creatine ratio (r = -0.50; p = 0.01). In contrast, three of the composite MR scores computed using regression models were strongly correlated with the EDSS scores (r range, 0.58 to 0.73; p range, 0.004 to 0.0001). The model that included T2 and T1 lesion volumes and brain D explained 34% of the EDSS variance; the model that included T2 and T1 lesion volumes and brain N-acetylaspartate/creatine ratio explained 36% of the EDSS variance; the model that included T1 lesion volume, brain D, and brain N-acetylaspartate/creatine ratio explained 53% of the EDSS variance. CONCLUSIONS: The results suggest that multiparametric MR models have the potential to provide powerful measures to monitor MS evolution.

Adult↗
PubMed2001

The T9176G mtDNA mutation severely affects ATP production and results in Leigh syndrome.

The authors identified a novel mtDNA mutation (T9176G) in the ATPase 6 gene in a family in which a 10-year-old girl had a severe neurodegenerative disorder, her elder sister had died of Leigh syndrome (LS), and a maternal uncle had a spinocerebellar disorder. Biochemical studies disclosed a reduced rate of ATP synthesis in skin fibroblast cultures from the proposita as the likely explanation of her severe illness. The findings expand the genetic variants associated with LS.

Adenosine Triphosphate↗
PubMed2001

A novel mutation in the Notch3 gene in an Italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: genetic and magnetic resonance spectroscopic findings.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary syndrome caused by mutations of the Notch3 gene, usually localized to exons 3 and 4. OBJECTIVES: To report a novel pathogenetic mutation occurring in exon 6 of the Notch3 gene, a location not previously recognized in patients with CADASIL, and to report the results of magnetic resonance spectroscopy in CADASIL. METHODS: Mutation analysis of the Notch3 gene was performed in 2 patients belonging to a large kindred manifesting CADASIL, as well as in 7 clinically unaffected members of the family and 200 control chromosomes. Proton magnetic resonance spectroscopy was used to estimate metabolite resonance intensities in the 2 affected subjects. RESULTS: Sequence analysis of the Notch3 gene showed a new missense mutation CGC-->TGC in codon 332 of exon 6, resulting in the replacement of an arginine residue with a cysteine. This mutation was never observed in the 7 unaffected members of the family and the 200 control chromosomes examined. Proton magnetic resonance spectroscopy showed a diffuse decrease in cerebral N-acetylaspartate, indicating the presence of widespread axonal damage. CONCLUSIONS: Our findings emphasize the role of direct DNA sequence analysis for the diagnosis of CADASIL. Moreover, the results of proton magnetic resonance spectroscopy suggest that widespread axonal damage may be an early finding of the disease.

Adult↗
PubMed2001

Pseudoxanthoma elasticum: Point mutations in the ABCC6 gene and a large deletion including also ABCC1 and MYH11.

Pseudoxanthoma elasticum (PXE) is a mendelian disorder characterized by calcification of elastic fibers in skin, arteries, and retina. It results in dermal lesions, arterial insufficiency and retinal hemorrhages, leading to macular degeneration. PXE is transmitted either as an autosomal dominant or recessive trait and several sporadic cases have been observed. Mutations in the ABCC6 gene have been identified very recently in patients. Here, we report on a large Italian family affected by pseudoxanthoma elasticum for which linkage analysis had pointed to a region encompassing markers D16S3069-D16S405-D16S3103; hemizygosity of marker D16S405 allowed us to detect a submicroscopic deletion of at least 900 kb involving ABCC6, ABCC1, and MYH11. Mutation analysis on the other allele of the family, as well as on two additional sporadic cases, revealed nonsense (Y227X, R518X, R1164X) and frame-shift (c.960delC) mutations in ABCC6 (MRP6) further confirming the role of this multi-drug resistance gene in the etiology of pseudoxanthoma elasticum. Furthermore, clinical re-examination of members of the family harboring the deletion led to the detection of additional features, potentially caused by the deletion of the MYH11 gene. In the course of the analysis five nonpathogenic variants were found in ABCC6: 1233T>C, 1245G>A, 1838 T>G (V614A), 1890C>G, and 3506+83C>A. Hum Mutat 18:85, 2001.

Adult↗
PubMed2001

Severe metabolic abnormalities in the white matter of patients with vacuolating megalencephalic leukoencephalopathy with subcortical cysts. A proton MR spectroscopic imaging study.

Vacuolating megalencephalic leukoencephalopathy (VML) with subcortical cysts is a neurodegenerative disorder clinically characterized by megalencephaly with onset in the first year of life, progressive ataxia, spasticity and relatively spared cognitive function. Conventional MRI findings consist of diffusely abnormal cerebral white matter with subcortical cysts. Recent single-voxel proton MR spectroscopy studies have shown mild metabolic abnormalities in the white matter. We report here a combined proton MR imaging and MR spectroscopic imaging (1H-MRSI) study on 2 new, unrelated patients with this rare disorder. 1H-MRSI examinations, which can provide simultaneously metabolic information from many different brain regions, showed inhomogeneous decreases in all normally detected metabolites with significant widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine and concomitant small increases in lactate in the white matter of both hemispheres. Metabolic abnormalities were milder in the frontal white matter and more severe in the posterior white matter. The 1H-MRSI pattern of the gray matter was normal in both patients. In one patient, a subsequent 1H-MRSI examination (performed 3 years after the first) confirmed the presence of widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine in the white matter. We conclude that severe metabolic abnormalities can be found in the white matter of VML patients. This suggests that, despite the apparently mild clinical course, a severe neurodegenerative process may occur in the white matter of these patients.

Adolescent↗
PubMed2001

Genetic leukoencephalopathies with unknown metabolic pathogenesis.

The authors describe the principal forms of genetic leucodystrophies with unknown metabolic pathogenesis, indicating their main clinical signs and the new findings concerning the molecular genetic that are useful for the laboratory confirmation of the clinical suspicion.

Demyelinating Diseases↗
PubMed2001

Alteration of haemostasis in non-metastatic gastric cancer.

BACKGROUND: Cancer is one of the most common acquired causes of venous thromboembolism. AIM: To evaluate haemostasis disorders in patients with non-metastatic gastric cancer. PATIENTS AND METHODS: We studied 11 patients with non-metastatic gastric cancer (9 males and 2 females, median age 54 years) and 20 healthy subjects (15 males and 5 females, median age 48 years) control. We measured prothrombin time, activated partial thromboplastin time, coagulation time, clot lysis time, fibrinogen, clotting factors (II, VII, VIII, IX, X), C protein, S protein, AT III, activated protein C resistance, prothrombin 1+2 fragment, tissue plasminogen activator and D-Dimer in all subjects. RESULTS: Fibrinogen plasma levels were significantly higher in patients with non-metastatic gastric cancer than in control group (505+/-24 mg/dl vs 336+/-30 mg/dl, p<0.001). We also found a significant increase in prothrombin 1+2 fragment plasma concentration compared with controls (3.8+/-0.6 nM vs 0.83+/-0.09 nM, p<0.001). Plasma D-dimer levels were 20-fold higher in patients with non-metastatic gastric cancer compared with controls (9.57+/-0.4 ng/dl vs 0.4+/-0.05 ng/dl, p<0.001). Also tissue plasminogen activator was significantly higher in gastric cancer patients than in controls (20.8+/-2.32 ng/ml vs 9.1+/-1.37 ng/ml, p<0.01). Finally clot lysis time was significantly accelerated in gastric cancer patients compared with control subjects (81+/-37 min vs 233+/-74 min, p<0.01). CONCLUSIONS: Patients with non-metastatic gastric cancer are at risk for thrombotic events due to the combined increase in fibrinogen plasma levels and thrombin formation.

Activated Protein C Resistance↗
PubMed2001

Cerebrotendinous xanthomatosis: heterogeneity of clinical phenotype with evidence of previously undescribed ophthalmological findings.

Cerebrontendinous xanthomatosis (CTX) is a rare autosomal recessive neurometabolic disease involving lipid metabolism. The classical phenotype is characterized by neurological dysfunction, tendon xanthomas and juvenile cataracts. Other ophthalmological findings have occasionally been reported. To gain more insight into the type and frequency of ophthalmological alterations in this multisystem metabolic disorder, we examined 13 CTX patients. Besides cataracts, found in all cases, the second most frequent ocular abnormality was paleness of the optic disk, which was found in 6 patients and was probably previously underestimated. Signs of premature retinal senescence were also observed. We discuss the possible relation between these ocular manifestations and the metabolic defect.

Adult↗
PubMed2001

Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract.

OBJECTIVE: To evaluate the effect of oral administration of selenium and zinc tablets in patients with cancer of the digestive tract during chemotherapy. DESIGN: A case-control, randomized study. SETTING: Medical Oncology, II University of Naples, Naples, Italy. SUBJECTS: A total of 60 patients (median age 55 y, range 46-61 y) with diagnosis of gut cancer were randomized in 1999. Patients were treated for 60 days with chemotherapy. INTERVENTIONS: Trace elements were measured by atomic absorption spectroscopy. The nutritional status of the patients was assessed by biochemical and bio-impedance analysis (BIA) parameters in basal condition and after 60 days of treatment. Oral administration of selenium and zinc in oral tablet form for 50 days was Se 200 microg/day (50 microg/tablet) and Zn 21 mg/day (7 mg/tablet). RESULTS: Both in the basal condition and at 60 days all patients were malnourished. Selenium and zinc concentrations were significantly lower (P < 0.01) whereas copper concentration was significantly higher (P < 0.01) in cancer patients than in control subjects. However, 21/30 (70%) of those treated with Se and Zn did not showed a further worsening of nutritional status and experienced a significant decrease of asthenia with an increase of appetite. On the other hand, 24/30 (80%) untreated patients had a significant decline of all parameters studied after 60 days (prealbumin, cholesterol, transferrin, P < 0.05 vs 0 time; total proteins, albumin/globulin ratio, P < 0.01 vs 0 time; fat-free mass, fat mass, Na+/K+ ratio, body mass index P < 0.05 vs 0 time; fat free mass/fat mass, total body water, extra cellular/intra cellular water, basal metabolic rate: P < 0.01 vs 0 time). CONCLUSIONS: Data indicate that Se and Zn supplementation may improve the clinical course of general conditions in patients with gut cancer. These effects of Se and Zn require confirmation in an independent trial of appropriate design before new public health recommendations regarding Se and Zn supplementation can be made.

Case-Control Studies↗
PubMed2001

Magnetic resonance imaging and spectroscopic changes in brains of patients with cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to an inherited defect in the metabolic pathway of cholesterol. Early diagnosis of the disease is particularly important as patients benefit from therapy with chenodeoxycholic acid. Although the disease is clinically characterized by the concomitant presence of tendon xanthomas, juvenile cataracts and progressive neurological impairment, clinical features may vary greatly. Neuroradiological studies have suggested that the bilateral abnormality of the dentate nuclei could be typical of this disease. However, this finding has been seen inconsistently on conventional MRI. The dynamic of the CNS pathology in CTX is complex, and whether demyelination or axonopathy has primary importance in the pathogenesis of CTX pathology is not known. To clarify both neuroradiological and pathological issues, we performed combined brain MRI and spectroscopy examinations on 12 CTX patients. On conventional MRIs, bilateral hyperintensities of the dentate nuclei were clearly seen in nine out of 12 patients on T(2) -weighted MRIs, but were evident in all patients using a FLAIR sequence. On proton magnetic resonance (MR) spectroscopy, significant decreases in N: -acetylaspartate resonance intensities (P: <0.0001) and increases in lactate MR signals (P<0.05) were found in the group of CTX patients in large volumes of interest localized above the lateral brain ventricles and in the cerebellar hemispheres. Cerebral values of N -acetylaspartate resonance intensities showed a close correlation with patients' disability (Spearman rank correlation = -0.78, P<0.005). These results suggest that MR abnormalities in the dentate nuclei may be evident consistently in patients with CTX. Proton MR spectroscopy data demonstrated widespread axonal damage (as shown by the decrease in N -acetylaspartate) and diffuse brain mitochondrial dysfunction (as shown by the increase in brain parenchymal lactate) in patients with CTX. The close correlation seen between values of the putative axonal marker N-acetylaspartate and patients' disability scores suggests that proton MR spectroscopy can provide a useful measure of disease outcome in CTX.

Adult↗
PubMed2001

Relationship of blood trace elements to liver damage, nutritional status, and oxidative stress in chronic nonalcoholic liver disease.

Trace elements are involved in chronic liver diseases because these elements may have a direct hepatic toxicity or may be decreased as a consequence of the impaired liver function, particularly in patients with alcoholic cirrhosis and/or malnutrition. In this study, we determined plasma and erythrocytes trace elements in 50 inpatients with nonalcoholic chronic liver disease (11 with biopsy-proven chronic hepatitis, 39 with cirrhosis [16 in stage A according to Child-Pugh criteria, 23 Child B+C]), and in a control group of 10 healthy subjects by the proton induced x-ray emission method. The relationship between trace element concentration and the extent of liver damage, the nutritional status (by anthropometric evaluations), and various blood markers of oxidative stress--reduced glutathione, total lipoperoxides and malonyldialdehyde--was investigated. We found that cirrhotics had a significant decrease of Fe, Zn, Se, and GSH levels in the plasma and of GSH and Se in the erythrocytes with respect to the control and chronic hepatitis groups. GSH levels were related to the degree of liver damage; a significant direct correlation was observed among Se, Zn, and GSH plasma values and between GSH and Se in the erythrocytes. The trace element decrease was, on the contrary, independent of the degree of liver function impairment and only partially affected by the nutritional status. Data indicate that liver cirrhosis, even if not alcohol related, induces a decrease of Se and Zn and that, in these patients, an oxidative stress is present, as documented by the significant correlation between Se and GSH. The plasma Br level was higher in cirrhotics with respect to the control and chronic hepatitis groups.

Adolescent↗
PubMed2001

MR brain imaging of fucosidosis type I.

SUMMARY: Fucosidosis is a rare autosomal recessive lysosomal storage disease with the main clinical findings of progressive neuromotor deterioration, seizures, coarse facial features, dysostosis multiplex, angiokeratoma corporis diffusum, visceromegaly, recurrent respiratory infections, and growth retardation. Fucosidosis type I rapidly evolves toward a progressive neurologic deterioration and death. We report MR imaging findings of the brain of three patients with fucosidosis type I, including previously unreported findings, to expand the knowledge of the neuroradiologic spectrum of the disease.

Atrophy↗