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Biomedical subjects

P Barone

Publications and source records attributed to P Barone.

At least 37 records · Page 2Linked to original sources

The status of dopamine nerve terminals in Parkinson's disease and essential tremor: a PET study with the tracer [11-C]FE-CIT.

Neuroimaging studies of the striatal dopamine transporter (DAT) are useful in the assessment of the dopaminergic system in Parkinson's disease (PD). We used positron emisson tomography (PET) and the tracer [11C]FE-CIT to measure DAT binding in the caudate nucleus and putamen of 31 patients with PD, 5 with essential tremor and 8 healthy control subjects. Of the patients with PD, 17 were drug naive, while the others were either on levodopa or dopamine agonist monotherapy. DAT binding was significantly reduced in the caudate nucleus and to a greater extent in the putamen of PD patients compared to both healthy controls and essential tremor individuals. No overlap was observed between putamen values in PD and normals. No differences were found between controls and essential tremor subjects. These data confirm that measurements of DAT binding can provide an accurate and highly sensitive measure of degeneration in the dopamine system in PD.

Carbon Radioisotopes↗

Stimulation of growth hormone release in multiple system atrophy, Parkinson's disease and idiopathic cerebellar ataxia.

Clonidine has been proposed to differentiate multiple system atrophy (MSA) from idiopathic Parkinson's disease (IPD), as it does not increase growth hormone (GH) release in MSA. We studied GH release in response to clonidine in 7 IPD patients, 6 MSA patients, 4 patients affected by idiopathic late-onset cerebellar ataxia (ILOCA) and 8 healthy controls. In addition, we investigated the effects of GH releasing hormone plus arginine (GHRH-Arg) on GH release in the same patients. Both clonidine and GHRH-Arg raised serum GH levels in all groups examined. Clonidine failed to differentiate MSA from IPD and ILOCA. GHRH-Arg showed a lower increase of serum GH in MSA patients than in other groups, even if such difference was not statistically significant. We suggest that stimulation of GH release with GHRH-Arg rather than clonidine could differentiate MSA from IPD and ILOCA, but this hypothesis would need to be confirmed by further investigations.

Adrenergic alpha-Agonists↗

Unawareness of dyskinesias in Parkinson's and Huntington's diseases.

We performed a clinical study to evaluate the unawareness of dyskinesias in patients affected by Parkinson's disease (PD) and Huntington's disease (HD). Thirteen PD patients with levodopa-induced dyskinesias and 9 HD patients were enrolled. Patients were asked to evaluate the presence of dyskinesias while performing specific motor tasks. The Abnormal Involuntary Movement Scale (AIMS) and Goetz dyskinesia rating scale were administered to determine the severity of dyskinesias. The Unified Parkinson's disease rating scale (UPDRS) and Unified Huntington's Disease Rating Scale (UHDRS) were used in PD and HD patients, respectively. In PD we found a significant negative relationship between unawareness score at standing and AIMS score and between unawareness score at hand pronation-supination and AIMS score for upper limbs. In HD we found a significant positive relationship between total unawareness score and UHDRS score and between total unawareness score and disease duration. In PD the unawareness seems to be inversely related with severity of dyskinesias, while in HD it is directly related to disease duration and severity.

Aged↗

[Cardiac involvement in Kawasaki disease. Our experience].

BACKGROUND: Kawasaki disease is an acute vasculitis of unknown cause that affects children under 5 years of age and in 20-25% of cases can cause coronary artery anomalies. Early therapy with intravenous gamma globulin and aspirin greatly decreases the risk of developing coronary anomalies, but sometimes coronary disease develops even in timely diagnosed and treated cases. METHODS: Personal experience in 41 children with Kawasaki disease is reported. Age was within three months and 5 years. All patients had electrocardiography and echocardiography at diagnosis, after 1 week, at the third, sixth, and eighth week, after six months and after 1 year from diagnosis. Echocardiographic cardiac anomalies were found only in 5 cases (12.19%). Average age in these cases was lower. RESULTS: In these cases coronary involvement developed in spite of early diagnosis and therapy (intravenous gamma globulin 400 mg/kg die and aspirin) electrocardiographic findings were not relevant or specific to coronary arteries anomaly. In three cases coronary anomalies regressed during the first year from diagnosis, the other two are still in the first year of follow-up. Nine children had a long term follow-up (6 to 9 years) and they were all normal except one with renal arteritis and another with slight mitral incompetence. CONCLUSIONS: The authors underline the role of clinical and instrumental follow-up that should be extended to all patients affected by Kawasaki disease with coronary anomalies even if early regressed.

Age Factors↗

Laminar distribution of neurons in extrastriate areas projecting to visual areas V1 and V4 correlates with the hierarchical rank and indicates the operation of a distance rule.

The directionality of corticocortical projections is classified as feedforward (going from a lower to higher hierarchical levels), feedback (interconnecting descending levels), and lateral (interconnecting equivalent levels). Directionality is determined by the combined criteria of the laminar patterns of the axon terminals as well as the cells of origins and has been used to construct models of the visual system, which reveals a strict hierarchical organization (Felleman and Van Essen, 1991; Hilgetag et al., 1996a). However, these models are indeterminate partly because we have no indication of the distance separating adjacent levels. Here we have attempted to determine a graded parameter describing the anatomical relationship of interconnected areas. We have investigated whether the precise percentage of labeled supragranular layer neurons (SLN%) in each afferent area after injection in either visual areas V1 or V4 determines its hierarchical position in the model. This shows that pathway directionality in the Felleman and Van Essen model is characterized by a range of SLN% values. The one exception is the projection of the frontal eye field to area V4, which resembles a feedforward projection. Individual areal differences in SLN% values are highly significant, and the number of hierarchical steps separating a target area from a source area is found to be tightly correlated to SLN%. The present results show that the hierarchical rank of each afferent area is reliably indicated by SLN%, and therefore this constitutes a graded parameter that is related to hierarchical distance.

Animals↗

Angular studies of potential electron emission in the interaction of slow ions with Al surfaces

We report energy distributions of electrons emitted from Al surfaces under impact by 1 keV Ar+ and 1-5 keV Ne+ ions. The variation of the energy distributions with the angle of incidence is different for both ions and provides information on the mechanism responsible for electron emission. For Ar+ electron emission results mainly from Auger neutralization, while for Ne+ an important emission mechanism is the decay of plasmon excitations. We find a transition between surface and bulk plasmon excitations as the energy of the ion is increased.

Journal Article↗

Accuracy of clinical diagnostic criteria for Friedreich's ataxia.

The accuracy of the diagnostic criteria for Friedreich's ataxia proposed by Harding and by the Quebec Cooperative Study on Friedreich's Ataxia was studied in 142 patients with progressive unremitting ataxia of autosomal recessive inheritance or sporadic occurrence. Eighty-eight patients received the molecular diagnosis of Friedreich's ataxia. Traditional diagnostic criteria are characterized by high specificity, but they yield a high number of false-negative diagnoses. We suggest three levels of diagnostic certainty: (1) possible Friedreich's ataxia, defined as sporadic or recessive progressive ataxia with (a) lower limb areflexia and dysarthria, Babinski sign, or electrocardiographic repolarization abnormalities, or (b) with lower limb retained reflexes and electrocardiographic repolarization abnormalities (95% sensitivity and 88% positive predictive value); (2) probable Friedreich's ataxia as defined by Harding's criteria (63% sensitivity and 96% positive predictive value) or by Quebec Cooperative Study on Friedreich's Ataxia criteria (63% sensitivity and 98% positive predictive value); (3) definite diagnosis, molecularly confirmed.

Adolescent↗

Bayesian estimation of relaxation times T(1) in MR images of irradiated Fricke-agarose gels.

The authors present a novel method for processing T(1)-weighted images acquired with Inversion-Recovery (IR) sequence. The method, developed within the Bayesian framework, takes into account a priori knowledge about the spatial regularity of the parameters to be estimated. Inference is drawn by means of Markov Chains Monte Carlo algorithms. The method has been applied to the processing of IR images from irradiated Fricke-agarose gels, proposed in the past as relative dosimeter to verify radiotherapeutic treatment planning systems. Comparison with results obtained from a standard approach shows that signal-to noise ratio (SNR) is strongly enhanced when the estimation of the longitudinal relaxation rate (R1) is performed with the newly proposed statistical approach. Furthermore, the method allows the use of more complex models of the signal. Finally, an appreciable reduction of total acquisition time can be obtained due to the possibility of using a reduced number of images. The method can also be applied to T(1) mapping of other systems.

Bayes Theorem↗

Non-uniformity of neocortex: areal heterogeneity of NADPH-diaphorase reactive neurons in adult macaque monkeys.

We have examined the distribution of cortical neurons in adult monkey cortex which stain for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), an enzyme which is involved in the synthesis of nitric oxide. In order to compare distributions across areas we employed a cortical unit defined as the radial column, which refers to the volume of cortex below 1 mm(2) of cortical surface. Numbers of labeled neurons per radial column generate areal density measurements either for the full thickness of the cortex or for individual layers. Measurements were made in six cortical regions (areas V1, V2, STS, auditory cortex, area 4 and area 6). NADPH-d stains nonpyramidal neurons which can be divided into two major groups. Type 1 neurons have large soma diameters, stain densely for NADPH-d and show few morphological variations both within and across areas. Type 2 neurons have small somata and short processes, and can be subdivided on the basis of soma size into dense and light staining categories. Both subcategories of type 2 neurons show significant areal variations in size. In each cortical area the majority of type 1 neurons are located in the white matter. Areal densities of type 1 neurons are minimal in areas V1 and V2, and twice as dense in the frontal cortex. Pairwise comparisons of areal densities among the six areas examined show that in a radial column throughout the full thickness of cortex, areas differ significantly from each other in 12/15 comparisons. Consideration of individual layers shows significant differences in 13/15 comparisons. Type 2 neurons are exclusively located in the cortical gray matter, and in all areas are considerably more numerous than type 1 neurons. Area V1 is unique it that it has up to three times the areal density found in any other cortical area. With reference to published laminar cell density counts our results show that the percentage of labeled NADPH-d neurons in individual layers of area V1 are significantly higher than in the other areas. The laminar distributions of type 1 and type 2 neurons show that each area has a unique profile of NADPH-d expression. The modular or columnar organization of the cortex, also referred to as the radial column hypothesis, is important for understanding both the development and function of the cortex. The present results show that radial columns in individual cortical areas possess distinctive patterns of NADPH-d expression. This important degree of areal heterogeneity of NADPH-d neurons has far reaching implications for both the development and functions of neocortical areas.

Animals↗

Directionality derived from differential sensitivity to monaural and binaural cues in the cat's medial geniculate body.

Azimuth tuning of high-frequency neurons in the primary auditory cortex (AI) is known to depend on binaural disparity and monaural spectral (pinna) cues present in broadband noise bursts. Single-unit response patterns differ according to binaural interactions, strength of monaural excitatory input from each ear, and azimuth sensitivity to monaural stimulation. The latter characteristic has been used as a gauge of neural sensitivity to monaural spectral directional cues. Azimuth sensitivity may depend predominantly on binaural disparity cues, exclusively on monaural spectral cues, or on both. The primary goal of this study was to determine whether each cortical response pattern corresponds to a similar pattern in the medial geniculate body (MGB) or whether some patterns are unique to the cortex. Single-unit responses were recorded from the ventral nucleus (Vn) and lateral part of the posterior group of thalamic nuclei (Po), tonotopic subdivisions of the MGB. Responses to free-field presentation of noise bursts that varied in azimuth and sound pressure level were obtained using methods identical to those used previously in field AI. Many units were azimuth sensitive, i.e., they responded well at some azimuths, and poorly, if at all, at others. These were studied further by obtaining responses to monaural noise stimulation, approximated by reversible plugging of one ear. Monaural directional (MD) cells were sensitive to the azimuth of monaural noise stimulation, whereas binaural directional (BD) cells were either insensitive to its azimuth or monaurally unresponsive. Thus BD and MD cells show differential sensitivity to monaural spectral cues. Monaural azimuth sensitivity could not be used to interpret the spectral sensitivity of predominantly binaural cells that exhibited strong binaural facilitation because they were either unresponsive or poorly responsive to monaural stimulation. The available evidence suggests that some such cells are sensitive to spectral cues. The results do not indicate the presence of any response types in AI that are not present in the MGB. Vn and Po contain similar classes of MD and BD cells. Because Po neurons project to the anterior auditory field, neurons in this cortical area also are likely to exhibit differential sensitivity to binaural disparity and monaural spectral cues. Comparison of these MGB data with a published report of cochlear nucleus (CN) single-unit azimuth tuning shows that MGB sensitivity to spectral cues is considerably stronger than CN sensitivity.

Acoustic Stimulation↗

Pergolide monotherapy in the treatment of early PD: a randomized, controlled study. Pergolide Monotherapy Study Group.

OBJECTIVE: To determine whether pergolide monotherapy provides symptomatic relief in early PD. BACKGROUND: Early treatment with dopamine agonists may reduce the risk of motor fluctuations, which are most likely linked to levodopa therapy. Pergolide, a D1-D2 dopamine agonist, has been studied as "add on" therapy in PD, but no controlled clinical trial studying the efficacy of pergolide monotherapy is available. METHODS: The efficacy and tolerability of pergolide were evaluated in a multicenter, double-blind, randomized, parallel-group, 3-month trial versus placebo. Patients with a diagnosis of idiopathic PD, a modified Hoehn & Yahr score of 1 to 3, and a score greater than 14 points on the Unified Parkinson's Disease Rating Scale (UPDRS) part III at baseline were enrolled in the study (pergolide, n = 53; placebo, n = 52). RESULTS: Patient characteristics at study entry were comparable in the two study groups. The pergolide group showed a significantly greater percent of responders (defined as a -30% decrease in UPDRS part III score at end point) compared with placebo (57% versus 17%; p < 0.001). Pergolide-treated patients experienced a significantly greater improvement than placebo-treated patients (p < 0.001) in UPDRS (overall, part II, and part III) score, Schwab & England score, and Clinical Global Impression improvement score. By the study end the mean dose of pergolide was 2.06 mg/day. Six patients in the pergolide group versus two patients in the placebo group discontinued the study because of treatment emergent side effects. CONCLUSION: This study suggests that pergolide monotherapy may be an efficacious and well-tolerated first-line treatment in patients with early-stage PD.

Aged↗

Nitrite- and peroxide-dependent oxidation pathways of dopamine: 6-nitrodopamine and 6-hydroxydopamine formation as potential contributory mechanisms of oxidative stress- and nitric oxide-induced neurotoxicity in neuronal degeneration.

In the presence of nitrite ions (NO(2)(-)) in phosphate buffer (pH 7. 4) and at 37 degrees C, dopamine was oxidized by a variety of hydrogen peroxide (H(2)O(2))-dependent enzymatic and chemical systems to give, in addition to black melanin-like pigments via 5, 6-dihydroxyindoles, small amounts of the potent neurotoxin 6-hydroxydopamine (1) and of 6-nitrodopamine (2), a putative reaction product of dopamine with NO-derived species. Treatment of 0. 5 or 1 mM dopamine with horseradish peroxidase (HRP) or lactoperoxidase (LPO) in the presence of 1 or 2 mM H(2)O(2) with NO(2)(-) at a concentration of 0.5-10 mM resulted in the formation of 1 and 2 in up to 8 and 2 microM yields, respectively, depending on the substrate concentration and the NO(2)(-):H(2)O(2) ratio. Nitration and hydroxylation of 0.1 mM dopamine was observed with 1 mM NO(2)(-) using HRP and the D-glucose/glucose oxidase system to generate H(2)O(2) in situ. In the presence of NO(2)(-)-, Fe(2+)-, or Fe(2+)/EDTA-promoted oxidations of dopamine with H(2)O(2) also led to the formation of 1 and 2, the apparent product ratios varying with peroxide concentration and the partitioning of the metal between EDTA and catecholamine chelates. In the presence of NO(2)(-), Fe(2+)-promoted autoxidation of dopamine gave 2 but no detectable 1. When injected into the brains of laboratory rats, 2 caused sporadic behavioral changes, indicating that it could elicit a neurotoxic response, albeit to a lower extent than 1. Model experiments using tyrosinase as an oxidizing system and mechanistic considerations suggested that formation of 2 does not involve reactive nitrogen radicals but results mainly from nucleophilic attack of NO(2)(-) to dopamine quinone. Generation of 1, on the other hand, may be derives from different H(2)O(2)-dependent pathways. Collectively, these results outline a complex interplay of NO(2)(-)- and peroxide-dependent oxidation pathways of dopamine, which may contribute to impair dopaminergic neurotransmission and induce cytotoxic processes in neurodegenerative disorders.

Animals↗

Otx genes in corticogenesis and brain development.

A large number of genes have been isolated in the last few years that seem to be involved in the processes of induction, specification and regionalization of the brain. The generation of mouse mutant models for such genes has provided a powerful tool of analysis into their in-vivo properties. Among these genes, Otx1 and Otx2 play a crucial role in several processes of brain morphogenesis. Otx2 is required in the early specification of the neuroectoderm destined to become the fore-midbrain, Otx1 is required mainly for correct corticogenesis, and both genes co-operate in patterning the developing brain through a gene-dosage dependent mechanism. Furthermore, an extensive functional equivalence occurs between the mammalian Otx genes and their Drosophila homolog, orthodenticle. This appears particularly fascinating when considering the huge differences between the brains of mice and flies. This review deals with the major aspects related to the involvement of Otx1 and Otx2 in the development of the mammalian brain and, in particular, of the cerebral cortex.

Animals↗

Idiopathic cerebellar ataxia associated with celiac disease: lack of distinctive neurological features.

OBJECTIVES: To determine the occurrence of celiac disease in a population of ataxic patients without definite diagnosis and to characterise distinctive features which may help to differentiate cerebellar ataxia with and without celiac disease. METHODS: Twenty four ataxic patients without definite diagnosis (group A) and 23 ataxic patients with definite diagnosis (group B) were screened for antigliadin (AGAs) and antiendomysium antibodies (EMAs). Patients with a positive AGA or EMA test underwent endoscopic biopsy of the duodenal mucosa. RESULTS: There was an increased prevalence of celiac disease in group A (3/24) compared with group B (0/23). None of the celiac patients presented gastrointestinal symptoms or malabsorption signs. None of the ataxic patients with celiac disease had early onset ataxia. CONCLUSIONS: Celiac disease is associated with ataxic syndromes without definite diagnosis, suggesting that it plays a part in the pathogenesis of some ataxic syndromes. The absence of distinctive neurological features in ataxic patients with celiac disease suggests that a search should be made for celiac disease markers in all ataxic patients without definite diagnosis.

Adult↗