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Biomedical subjects

L Frattola

Publications and source records attributed to L Frattola.

At least 19 recordsLinked to original sources
PubMed2006

Extracorporeal photochemotherapy: a safety and tolerability pilot study with preliminary efficacy results in refractory relapsing-remitting multiple sclerosis.

Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure consisting of autologous reinfusion of peripheral blood mononuclear cells (PBMC) after direct exposure to 8-methoxy-psoralen and UV-A. It has been described as a successful treatment for different T-cell-mediated diseases and preliminary results suggest that ECP might be effective in the treatment of relapsing-remitting multiple sclerosis, but does not significantly alter the course of the progressive form of MS. In this study, we report the safety data and some preliminary efficacy evidence obtained using ECP in the treatment of five patients with refractory relapsing-remitting (RR) MS: in most cases ECP induced a reduction in the relapse rate and an EDSS stabilisation, with an apparent general MRI stabilisation. In conclusion, our results confirm ECP safety and tolerability and suggest that this treatment might be useful as a therapeutic alternative in the subgroup of RRMS patients not responsive to or not eligible for traditional immunomodulating or immunosuppressive treatments.

Adult↗
PubMed2004

Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease: facts and uncertainties underlying the causal link between animal and human diseases.

Following an outbreak of bovine spongiform encephalopathy (BSE) in dairy cows in the United Kingdom (UK), 153 definite and probable human cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been reported, almost exclusively in the UK. Although exposure to the BSE agent is the most plausible interpretation for the occurrence of nvCJD, the causal link between the BSE prion and nvCJD is still debated. This review discusses the pros and cons of nvCJD as a separate nosographic entity, the scientific basis for a correlation between BSE and nvCJD, the validity of the current diagnostic criteria for CJD and nvCJD, the contribution of epidemiology to the detection of a causal relation between BSE and nvCJD, and the present and future directions of the epidemiological research on BSE, CJD and nvCJD.

Animals↗
PubMed2003

Cognitive [correction of cognitve] estimation: comparison of two tests in nondemented parkinsonian patients.

The Time and Weight Estimation test (STEP) and the Cognitive Estimation Task (CET) are two recently devised tests for the assessment of cognitive estimation. In the present study, we compared their performance in 30 non-demented idiopathic parkinsonian (PD) patients, also evaluated with the Frontal Assessment Battery (FAB) as an index of executive impairment, with the aim of verifying the putative frontal circuitry of cognitive estimation processes. Six patients (20%) showed a pathological performance on either or both tests. After division of the PD sample into tertiles based on the FAB score, no significant difference was detected by either estimation test. Furthermore, the two questionnaires were unrelated to each other. Thus, deficits of cognitive estimation ability appear to be mild in PD without dementia and do not correlate with executive impairment. Unexpectedly, the CET and the STEP seem to have no unique underlying construct.

Aged↗
PubMed2003

Assessing clinically relevant cognitive decline: preliminary data on a new method.

Physiological age-related cognitive decline, practice effect and regression to the mean may interfere with the interpretation of psychometric changes between subsequent neuropsychological evaluations. The standardized regression-based (SRB) change score allows investigators to define clinically relevant cognitive change on an individual basis controlling for these confounding factors. We performed a preliminary study to test its applicability and usefulness in the neuropsychological diagnosis of dementia. We derived a regression equation for the tests of a widely used Italian battery for global cognitive assessment, the Mental Deterioration Battery, in a sample of 20 normal elderly and we tested the potential clinical application of the SRB methodology in two cases of questionable dementia.

Aged↗
PubMed2003

Physical anhedonia in Parkinson's disease.

Anhedonia is the inability to experience physical or social pleasure. Its physical component is hypothesised to be due to dysfunction of a dopaminergic frontotemporal-subcortical circuit and has never been investigated as a possible affective complication of Parkinson's disease (PD). The aim of this study was to formally assess prevalence and correlates of physical anhedonia in PD patients compared with normal controls. Twenty five people with PD and 25 matched controls were administered a psychometric battery exploring mainly executive functions and mood. Hedonic tone was assessed using Chapman's Physical Anhedonia Scale. PD patients also underwent MRI linear measurement of frontal structures. Anhedonia levels were significantly higher in PD patients with respect to controls, although not extremely elevated; prevalence rate was 40% for parkinsonians, while no anhedonics were found among controls. Clinical, neuropsychological, and quantitative neuroradiological features did not show any significant correlation with physical anhedonia. Physical anhedonia appears to be a relatively frequent, although mild, affective disturbance of PD, independent from neurological, frontal, and depressive aspects.

Aged↗
PubMed2002

Screening cognitive decline in dementia: preliminary data on the Italian version of the IQCODE.

The IQCODE is a retrospective questionnaire for caregivers about changes which occurred in a patient's cognitive and functional efficiency in the previous 10 years of life. Previous studies demonstrated the validity of the IQCODE for the screening of dementia similar to that of traditional cognitive screening tests, with the additional advantage of allowing the detection of cognitive change, rather than just cognitive impairment. The present paper deals with the preliminary results of the validation of the Italian version of the questionnaire in a sample of 45 mild to severely demented patients and 13 patients with mild cognitive impairment (MCI), compared to 20 cognitively intact elderly subjects. The IQCODE demonstrated satisfactory discriminative power for dementia as well as for MCI and a good correlation with the MMSE.

Aged↗
PubMed2001

Increased glutamate in CSF and plasma of patients with HIV dementia.

BACKGROUND: Experimental evidence suggests that excitotoxicity might play a major role in HIV-induced neurodegeneration. However, few studies have investigated the role of endogenous glutamate in patients with HIV dementia. OBJECTIVE: To analyze CSF and plasma glutamate levels in 30 patients with AIDS with different dementia severity compared with 10 patients with other neurologic disorders, 11 healthy control subjects, and 10 patients with Alzheimer-type dementia. METHODS: CSF and plasma glutamate levels were measured by reverse-phase high-performance liquid chromatography followed by fluorometric analysis. RESULTS: Glutamate CSF levels were increased fivefold in the patients with HIV vs normal control subjects (p = 0.001), patients with Alzheimer-type dementia (p < 0.0001), and patients with other neurologic disorders (p < 0.01). CSF glutamate levels were also related to the degree of dementia (p < 0.02) and brain atrophy (p < 0.002). Plasma levels were also higher in the patients with HIV (p < 0.0001) but did not correlate with either clinical or imaging features. CONCLUSION: Increased CSF glutamate may originate within the CNS and may play a pathogenetic role in HIV dementia, thus supporting the treatment of these patients with glutamate receptor antagonists.

AIDS Dementia Complex↗
PubMed2001

Decreased platelet glutamate uptake in patients with amyotrophic lateral sclerosis.

Decreased glutamate uptake and a loss of the astrocytic glutamate transporter EAAT2 (GLT-1) have been shown in spinal cord and motor cortex of patients with ALS. Because platelets express the three major glutamate transporter subtypes, including GLT-1, and possess a high-affinity glutamate uptake, the authors investigated glutamate uptake in platelets from patients with ALS and controls. A 43% reduction of high-affinity glutamate uptake rate (p < 0.0001) was observed in patients with ALS compared with normal controls and chronic neurologic disorder patients, suggesting a systemic impairment of glutamate uptake in ALS.

Adult↗
PubMed2001

Decreased platelet glutamate uptake and genetic risk factors in patients with Parkinson's disease.

Genetic risk factors seem to play a role in sporadic Parkinson's disease (PD), maybe triggering oxidative stress and excitotoxicity within substantia nigra. However, genetic factors act at systemic level: reduced activity of mitochondrial enzymes and decreased glutamate uptake have been shown in platelets from PD patients. In this study we investigated glutamate uptake in platelets from 38 sporadic PD patients, 13 patients with parkinsonian syndromes and 28 controls and assessed polymorphisms of alpha-synuclein and ApoE genes. A 48% reduction of glutamate uptake p)<0.0001) was observed in PD patients which, with respect to control groups, correlated with the disease severity (r = -0.44, p < 0.05). Genetic studies of this population did not show differences between PD and controls, nor correlations with platelet glutamate uptake.

Apolipoproteins E↗
PubMed2001

Physiologic study of the subthalamic volume.

Deep brain stimulation (DBS) obtains good control of advanced PD symptoms. Chronic stimulation of Stn may alleviate rigidity, dyskinesia and tremor. Anatomical and functional intraoperative mapping are mandatory to obtain careful target localisation. Per-operative macrostimulation was carried out in 22 patients undergoing bilateral DBS in Stn; a volume 6 mm above to 4 mm below Stn was explored. Positive, collateral and adverse effects were recorded every 2 mm. Results obtained during acute stimulation were correlated to anatomical data from stereotactic atlases. Our findings suggest a volume, encompassing the zona incerta, Forel's fields and the lowermost part of anterior thalamus, functionally homogeneous to Stn. In fact, the stimulation of this volume obtains reduction of PD symptoms comparable to Stn.

Aged↗
PubMed2001

Nerve growth factor and transforming growth factor-beta serum levels in acute stroke patients. Possible involvement of neurotrophins in cerebrovascular disease.

BACKGROUND AND PURPOSE: Experimental evidence indicates cytokine and neurotrophin production in brain tissue after stroke. Since neurotrophins may also be released from blood cells, we measured nerve growth factor (NGF) and transforming growth factor (TGF)-beta serum levels in 40 patients at various times after stroke and compared them to those in 20 healthy controls. METHODS: Venous blood was obtained 1, 4, 10, 30 and 90 days after stroke and NGF and TGF-beta serum levels were measured by commercial ELISA. Values at each time were correlated with stroke severity, assessed using the National Institute of Health Stroke Scale, and with lesion volume, calculated using Cavalieri's direct estimator on a computerized tomography scan performed 5 days after stroke. RESULTS AND CONCLUSIONS: Although no significant differences between the two groups were demonstrated, in stroke patients, serum neurotrophins were significantly associated with clinical and neuroradiological parameters of brain injury and positively correlated with each other in the acute phases of stroke, suggesting that stroke may modulate peripheral neurotrophin levels.

Humans↗
PubMed2001

Immunomodulating effects of extracorporeal photochemotherapy in rat experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a well-established model of human multiple sclerosis that is commonly used to evaluate the possible effectiveness of new treatments in this disease. Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure currently used in several non-neurological diseases that, like multiple sclerosis, are likely to be due to T-cell-mediated autoimmunity. In this study we examined the effect of ECP using the EAE paradigm in the Lewis rat. In our model, ECP induced a significant modulation in peripheral blood T-cell distribution, changes which are typical of EAE. Remarkably, this effect was closely correlated with the clinical and pathological results, which showed reduced severity of the disease in the ECP-treated EAE animals vs. the EAE alone rats. We conclude that ECP induces modifications in the immunological events that occur during the course of EAE in rats, thus giving support to the hypothesis that it could be used in the treatment of multiple sclerosis.

Adjuvants, Immunologic↗
PubMed2000

Effect on the peripheral nervous system of systemically administered dimethylsulfoxide in the rat: a neurophysiological and pathological study.

The issue of dimethylsulfoxide (DMSO) neurotoxicity is an important one, given its wide use in experimental toxicology as a solvent for hydrophobic substances. We examined the effect of the intraperitoneal administration of different DMSO solutions (1.8-7. 2%) on the peripheral nervous system of Wistar rats treated for 10 consecutive days and followed-up for an additional 45 days. DMSO administration induced a dose-dependent reduction in nerve conduction velocity, with complete recovery occurring in the follow-up. No structural changes were found in the sciatic nerve at 1.8% and 3.6% DMSO concentrations, suggesting that the mechanism of action of DMSO involves a functional impairment (i.e. conduction block) similar to that already described for this substance in isolated systems. However, when DMSO was administered at the 7.2% concentration, evident structural changes were observed in the sciatic nerve, with myelin disruption and uncompacted myelin lamelle. The neurophysiological and pathological changes observed in our study are severe enough to merit careful consideration in the course of experimental studies involving DMSO as a solvent for drugs which are under evaluation for their potential neurotoxicity.

Animals↗
PubMed2000

Creutzfeldt-Jakob disease with a novel four extra-repeat insertional mutation in the PrP gene.

OBJECTIVE: To investigate the role of a short insertional mutation in the prion protein (PrP) gene (PRNP) in prion disease pathogenesis. BACKGROUND: The genetic forms of Creutzfeldt-Jakob disease (CJD) are associated with point or insertional mutations in PRNP. Whereas patients with five, six, seven, eight, and nine extra octapeptide repeats show an autosomal dominant pattern of inheritance and features of CJD, Gerstmann-Sträussler-Scheinker disease, or atypical dementia, patients with one, two, or four extra repeats have typical CJD and lack a family history of neurologic disorder. METHODS: A genetic, neuropathologic, and biochemical study was carried out in a 65-year-old patient with clinical features of sporadic CJD. RESULTS: A novel four extra-repeat insertional mutation of PRNP was found in the patient and in his 59-year-old healthy sister. The patient showed spongiosis, nerve cell loss, and gliosis associated with diffuse PrP immunoreactivity in the cerebral cortex, subcortical gray structures, and cerebellum. A peculiar aspect was the presence of focal PrP deposits in the basal ganglia and hypothalamus, superimposed to diffuse PrP immunoreactivity. The biochemical analysis revealed that both mutant and wild-type PrP participated in the pathologic process, and that the protease-resistant core of the altered PrP isoforms was distinct from that observed in sporadic, acquired, and other genetic forms of CJD. CONCLUSION: These findings support the view that the four extra-repeat insertion in PRNP is a pathogenic mutation with low penetrance rather than a benign polymorphism, and suggest that this mutation results in the formation of a distinct PrP conformer.

Aged↗
PubMed2000

Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results of a multicentre, randomized, double-blind, placebo-controlled study.

INTRODUCTION: A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of alpha-dihydroergocryptine (alpha-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable. PATIENTS AND METHODS: Sixty-two patients (32 males, 30 females, mean age +/- SD 64 +/- 10) were randomized to alpha-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8 +/- 9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample. RESULTS: The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, alpha-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, alpha-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (alpha-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of alpha-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between alpha-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent. CONCLUSION: The results indicate that alpha-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients.

Dihydroergotoxine↗
PubMed2000

Glutamate uptake is decreased in platelets from Alzheimer's disease patients.

Because excitotoxicity may be involved in neurodegeneration in Alzheimer's disease, we investigated possible modifications of platelet glutamate uptake in AD patients. High-affinity glutamate uptake was studied in platelets from 35 Alzheimer's disease patients, 10 multi-infarct dementia patients, and 35 age-matched normal controls; it was decreased by 40% in platelets from Alzheimer's disease patients compared with controls and with multi-infarct dementia patients. Platelet glutamate uptake could be used as peripheral marker of glutamatergic involvement and as adjunctive diagnostic tool in Alzheimer's disease patients.

Aged↗