Investigating the Association of Wallerian Degeneration and Diaschisis After Ischemic Stroke With BOLD Cerebrovascular Reactivity.

INTRODUCTION: Wallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke. They may, however, share common neurophysiological denominators, since they are both related to disruption of fiber tracts and brain atrophy over time. Therefore, with advanced multimodal neuroimaging, we investigate Wallerian degeneration and its association with diaschisis. METHODS: In order to determine different characteristics of Wallerian degeneration, we conducted examinations on seventeen patients with chronic unilateral ischemic stroke and persisting large vessel occlusion, conducting high-resolution anatomical magnetic resonance imaging (MRI) and blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) tests, as well as Diamox 15(O)-H2O-PET hemodynamic examinations. Wallerian degeneration was determined using a cerebral peduncle asymmetry index (% difference of volume of ipsilateral and contralateral cerebral peduncle) of more than two standard deviations away from the average of age-matched, healthy subjects (Here a cerebral peduncle asymmetry index > 11%). Diaschisis was derived from BOLD-CVR to assess the presence of ipsilateral thalamus diaschisis and/or crossed cerebellar diaschisis. RESULTS: Wallerian degeneration, found in 8 (47%) subjects, had a strong association with ipsilateral thalamic volume reduction (r 2 = 0.60) and corticospinal-tract involvement of stroke (p < 0.001). It was also associated with ipsilateral thalamic diaschisis (p = 0.021), No cerebral peduncular hemodynamic differences were found in patients with Wallerian degeneration. In particular, no CBF decrease or BOLD-CVR impairment was found. CONCLUSION: We show a strong association between Wallerian degeneration and ipsilateral thalamic diaschisis, indicating a structural pathophysiological relationship.

Symbiotic, low-temperature, and scalable synthesis of bi-magnetic complex oxide nanocomposites.

Functional oxide nanocomposites, where the individual components belong to the family of strongly correlated electron oxides, are an important class of materials, with potential applications in several areas such as spintronics and energy devices. For these materials to be technologically relevant, it is essential to design low-cost and scalable synthesis techniques. In this work, we report a low-temperature and scalable synthesis of prototypical bi-magnetic LaFeO3-CoFe2O4 nanocomposites using a unique sol-based synthesis route, where both the phases of the nanocomposite are formed during the same time. In this bottom-up approach, the heat of formation of one phase (CoFe2O4) allows the crystallization of the second phase (LaFeO3), and completely eliminates the need for conventional high-temperature annealing. A symbiotic effect is observed, as the second phase reduces grain growth of the first phase, thus yielding samples with lower particle sizes. Through thermogravimetric, structural, and morphological studies, we have confirmed the reaction mechanism. The magnetic properties of the bi-magnetic nanocomposites are studied, and reveal a distinct effect of the synthesis conditions on the coercivity of the particles. Our work presents a basic concept of significantly reducing the synthesis temperature of bi-phasic nanocomposites (and thus also the synthesis cost) by using one phase as nucleation sites for the second one, as well as using the heat of formation of one phase to crystallize the other.

Controlling magnetic coupling in bi-magnetic nanocomposites.

Magnetic nanocomposites constitute a vital class of technologically relevant materials, in particular for next-generation applications ranging from biomedicine, catalysis, and energy devices. Key to designing such materials is determining and controlling the extent of magnetic coupling in them. In this work, we show how the magnetic coupling in bi-magnetic nanocomposites can be controlled by the growth technique. Using four different synthesis strategies to prepare prototypical LaFeO3-CoFe2O4 and LaFeO3-Co0.5Zn0.5Fe2O4 nanocomposite systems, and by performing comprehensive magnetic measurements, we demonstrate that the final material exhibits striking differences in their magnetic coupling that is distinct to the growth method. Through structural and morphological studies, we confirm the link between the magnetic coupling and growth methods due to distinct levels of particle agglomeration at the very microscopic scale. Our studies reveal an inverse relationship between the strength of magnetic coupling and the degree of particle agglomeration in the nanocomposites. Our work presents a basic concept of controlling the particle agglomeration to tune magnetic coupling, relevant for designing advanced bi-magnetic nanocomposites for novel applications.

Tunable single-phase magnetic behavior in chemically synthesized AFeO3-MFe2O4 (A = Bi or La, M = Co or Ni) nanocomposites.

The properties of magnetic nanocomposites rely strongly on the interplay between those of the constituent components. When the individual components themselves are complex systems belonging to the family of correlated electron oxide systems which typically exhibit exotic physical properties, it becomes nontrivial to customize the properties of the nanocomposite. In this paper, we demonstrate an easy, but effective method to synthesize and tune the magnetic properties of nanocomposites consisting of correlated electron oxide systems as the individual components. Our method is based on a novel synthesis technique by which the two components of the nanocomposite can be directly integrated with each other, yielding homogeneous samples on the nanoscale with magnetic behavior reminiscent of a single phase. We illustrate our method using multiferroic BiFeO3 (BFO) and LaFeO3 (LFO) as the major phase (i.e., matrix), and MFe2O4 (M = Co2+ or Ni2+) as the embedded magnetic phase. Furthermore, we show that by a proper selection of the second phase in the nanocomposite, it is possible to customize the magnetic properties of the matrix. We illustrate this by choosing CoFe2O4 and NiFe2O4, two oxides with widely differing magnetic anisotropies, as the embedded phase, and demonstrate that the coercivity of BFO and LFO can be increased or decreased depending on the choice of the embedded phase in the nanocomposite.

The interplay between single particle anisotropy and interparticle interactions in ensembles of magnetic nanoparticles.

This paper aims to analyze the competition of single particle anisotropy and interparticle interactions in nanoparticle ensembles using a random anisotropy model. The model is first applied to ideal systems of non-interacting and strongly dipolar interacting ensembles of maghemite nanoparticles. The investigation is then extended to more complex systems of pure cobalt ferrite CoFe2O4 (CFO) and mixed cobalt-nickel ferrite (Co,Ni)Fe2O4 (CNFO) nanoparticles. Both samples were synthetized by the polyol process and exhibit the same particle size (DTEM ≈ 5 nm), but with different interparticle interaction strengths and single particle anisotropy. The implementation of the random anisotropy model allows investigation of the influence of single particle anisotropy and interparticle interactions, and sheds light on their complex interplay as well as on their individual contribution. This analysis is of fundamental importance in order to understand the physics of these systems and to develop technological applications based on concentrated magnetic nanoparticles, where single and collective behaviors coexist.

Optimising the magnetic performance of Co ferrite nanoparticles via organic ligand capping.

Ferrofluids of CoFe2O4 nanoparticles are gaining increasing interest due to their enhanced heating performance in biomedical applications (e.g. in magnetic hyperthermia as mediators for cancer treatment) or in energy applications (e.g. magneto-thermo-electric applications). Until now, the effect of an organic surfactant on the magnetic particle behaviour has been unintentionally overlooked. Here, we present the counterintuitive magnetic effect of two representative organic ligands: diethylene glycol (DEG) and oleic acid (OA) bonded at the surface of small (∼5 nm in size) CoFe2O4 particles. The combined results of the bulk dc susceptibility, local-probe Mössbauer spectroscopy and physical modelling, which is based on electronic structure calculations and Monte Carlo simulations, reveal the effect of different ionic distributions of the particles due to the different surfactant layers on their magnetic behaviour. They result in an unexpected increase of the saturation magnetisation and the blocking temperature, and a decrease of the coercive field of DEG coated CoFe2O4 nanoparticles. Our work provides a pathway for the production of colloidal assemblies of nanocrystals for the engineering of functional nano-materials.

Studying nanoparticles' 3D shape by aspect maps: Determination of the morphology of bacterial magnetic nanoparticles.

Magnetic nanoparticles (MNPs) are widely investigated due to their potential use in various applications, ranging from electronics to biomedical devices. The magnetic properties of MNPs are strongly dependent on their size and shape (i.e., morphology), thus appropriate tools to investigate their morphology are fundamental to understand the physics of these systems. Recently a new approach to study nanoparticle morphology by Transmission Electron Microscopy (TEM) analysis has been proposed, introducing the so-called Aspect Maps (AMs). In this paper, a further evolution of the AM method is presented, allowing determination of the nanoparticles' 3D shape by TEM image. As a case study, this paper will focus on magnetite nanoparticles (Fe3O4), with a mean size of ∼45 nm extracted from Magnetospirillum gryphiswaldense magnetostatic bacteria (MTB). The proposed approach gives a complete description of the nanoparticles' morphology, allowing estimation of an average geometrical size and shape. In addition, preliminary investigation of the magnetic properties of MTB nanoparticles was performed, giving some insight into interparticle interactions and on the reversal mechanism of the magnetization.

Designing new ferrite/manganite nanocomposites.

Two kinds of nanocomposites of transition metal oxides were synthesized and investigated. Each nanocomposite comprises nanoparticles of La0.67Ca0.33MnO3 and CoFe2O4 in similar volume fractions, however arranged with different morphologies. The temperature-dependent magnetic and electrical properties of the two systems are found to greatly differ, suggesting different degrees of interaction and coupling of their constituents. This is confirmed by magnetic field-dependent experiments, which reveal contrasted magnetization reversal and magnetoresistance in the systems. We discuss this morphology-physical property relationship, and the possibility to further tune the magnetism and magneto-transport in such nanocomposites.

Evolution of the magnetic structure with chemical composition in spinel iron oxide nanoparticles.

Magnetic properties of iron oxide nanoparticles with spinel structure are strictly related to a complex interplay between cationic distribution and the presence of a non-collinear spin structure (spin canting). With the aim to gain better insight into the effect of the magnetic structure on magnetic properties, in this paper we investigated a family of small crystalline ferrite nanoparticles of the formula CoxNi1-xFe2O4 (0 ≤x≤ 1) having equal size (≈4.5 nm) and spherical-like shape. The field dependence of magnetization at low temperatures indicated a clear increase of magnetocrystalline anisotropy and saturation magnetization (higher than the bulk value for CoFe2O4: ∼130 A m(2) kg(-1)) with the increase of cobalt content. The magnetic structure of nanoparticles has been investigated by Mössbauer spectroscopy under an intense magnetic field (8 T) at a low temperature (10 K). The magnetic properties have been explained in terms of an evolution of the magnetic structure with the increase of cobalt content. In addition a direct correlation between cationic distribution and spin canting has been proposed, explaining the presence of a noncollinear spin structure in terms of superexchange interaction energy produced by the average cationic distribution and vacancies in the spinel structure.

Papillary glioneuronal tumor: case report and review of literature.

Papillary glioneuronal tumor (PGNT) is a recently described central nervous system neoplasm that mostly occurs in the supratentorial system, adjacent to the lateral ventricles. In 2007, WHO classified PGNT as grade I neuronal-glial tumor because of the characteristic papillary architecture and bipartite (astrocytic and neuronal/neurocytic) cell population. As a newly established entity of mixed glioneuronal tumor family, PGNT attracted extensive attention recently. In our report we discuss the clinical, neuroradiological and surgical features. The final result is compared with literature data.

A rare localization of cerebral venous sinus thrombosis. Case report.

In this work the Authors report their experience on the treatment of a case of cavernous venous sinus thrombosis. The diagnosis is clinical and neuroradiological, CT, MRN, cerebral angiography and orbital venography have aided in establishing the diagnosis during life. Very interesting is the therapeutic approach.

Internal haemorrhagic pachymeningiosis: specific disease or complication of chronic subdural hematoma? Report of five cases surgically treated and literature review.

BACKGROUND: Internal haemorrhagic pachymeningiosis (IHP) is a rare disease characterized by a fibrous thickening and inflammatory infiltration in dural space mimicking chronic subdural hematoma. The pathogenesis of IHP is not entirely clear yet and treatment is still controversial. OBJECTIVE: We want to emphasize the importance of differentiating pachymeningiosis from chronic subdural hematoma as distinct pathological entities. PATIENTS AND METHODS: The records of five selected cases of IHP histologically confirmed were reviewed, focusing onset, neuroimaging, surgery and outcomes. CONCLUSIONS: IHP is most likely underestimated. Only through multidisciplinary approach it is possible to plane the proper therapeutic strategy. The diagnosis of IHP is confirmed by definitive histology but in some cases is possible with intraoperative frozen section.

Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

Conversion from thrice daily to twice daily administration of gabapentin (GBP) in partial epilepsy: analysis of clinical efficacy and plasma levels.

Gabapentin has been administered in placebo-controlled studies with a thrice daily (T.I.D.) schedule, because of its short half-life. However, clinical efficacy does not seem strictly related to plasma levels: a twice daily (B.I.D.) schedule might therefore be possible. The aim of our study was to verify if the conversion from a T.I.D. to a B.I.D. regimen affected the efficacy and safety of gabapentin therapy. Out of 171 patients treated with add-on gabapentin, we selected 29 stable responders, who were followed for three months with a T.I.D. schedule and then switched to B.I.D. regimen for further three months. Seizure number, side-effects and trough plasma levels of gabapentin were collected during both periods. Gabapentin mean dose was 2117.2 mg/day. Mean number of seizures/months was: 4.2 at baseline, 1.0 during the T.I.D., and 0.9 during the B.I.D. period. Mean trough plasma level of gabapentin was 5.9 microgram/ml during the T.I.D. and 5.2 microgram/ml during the B.I.D. period. Twelve side-effects were reported by 11 patients during the T.I.D. and 6 by 5 patients during the B.I.D. period., sedation and vertigo were the most frequent in both. Results of our study suggest that gabapentin can be administered safely and effectively either with a T.I.D. and a B.I.D. regimen.

Antiandrogens: a summary review of pharmacodynamic properties and tolerability in prostate cancer therapy.

This article provides a summary of the pharmacodynamic properties of major antiandrogens as well as an extensive review of their tolerability. Presently there are two classes of androgen receptor antagonists: the so-called pure, non-steroidal antiandrogens which include flutamide, nilutamide and the more recent bicalutamide and the steroidal antiandrogens cyproterone acetate, megestrol acetate and WIN 49596. Although non steroidal and steroidal compounds have been found to be equally effective in the treatment of prostate cancer presently no studies comparing the use of steroidal or non steroidal antiandrogens with chemical or surgical castration have evaluated quality of life per se. The only advantage of cyproterone acetate on pure antiandrogens seems to be the low incidence of hot flushes; a commonly reported adverse effect of androgen ablative therapy. However, hepatotoxicity associated with long term daily doses of 300 mg daily and the unacceptably high incidence of cardiovascular side effects (10%) should restrict its use to patients who are intolerant of pure antiandrogen compound. In contrast to steroidal compound nonsteroidal compounds let sexual potency to be retained, which is an important consideration with respect to the quality of life of some patients and, at present, the main indication for monotherapy with the pure antiandrogens. As regard as pure antiandrogens clinically important adverse events including gastrointestinal events, particularly diarrhea and occasional disturbances of liver function related to flutamide treatment and antabuse effect, problems with light-dark adaptation and rare interstitial pneumonitis related to nilutamide indicates the bicalutamide, due to its better tolerability profile, together with its once-daily oral administration regimen, could be considered the antiandrogen of first choice in the treatment of prostatic cancer.

Correlations of topographical EEG features with clinical severity in mild and moderate dementia of Alzheimer type.

Quantitative electroencephalography (qEEG) and the Folstein Mini Mental State examination (MMSE) were obtained from 31 patients affected by probable dementia of Alzheimer's type (DAT). qEEG data were examined both by spectral analysis (Fast Fourier Transformation) and by single frequency band topographical centroid, and compared with those of 24 healthy subjects of the same age group. DAT patients were found to have higher absolute power in the slow (delta and theta) frequency bands. Quantitative topographical assessment showed significantly more anteriorly located centers of gravity for the alpha and beta activity. Only alpha anteriorization was correlated with the degree of cognitive impairment as measured by the global deterioration scale and MMSE. It is concluded that quantitative topographical assessment was successful for the statistical handling of the EEG power maps, and to identify a potential parameter for the functional staging of the disease.

Decreased EEG microstate duration and anteriorisation of the brain electrical fields in mild and moderate dementia of the Alzheimer type.

Spatially oriented segmentation allows researchers to break down the continuous stream of the ongoing EEG into microstates with stable topography of the brain electrical landscapes. The resulting microstates were shown to be related to conscious mental experience as well as to psychiatric disorders typically associated with thought disorders. In the present study, the microstates of the resting EEG of patients presenting with mild or moderate probable dementia of the Alzheimer type (DAT) were investigated. A significant anteriorisation of the centers of gravity of the microstate fields, an increase of the microstates' optimal window size and a reduced duration of sustained microstates were found. These differences were statistically more robust than the typical changes in the frequency domain (diffuse slowing) and were significantly correlated with the cognitive decline. The adaptive spatial segmentation into microstates is discussed as a method to extract meaningful EEG parameters for the early diagnosis and staging of Alzheimer's disease.

Brain electrical activity (quantitative EEG and bit-mapping neurocognitive CNV components), psychometrics and clinical findings in presenile subjects with initial mild cognitive decline or probable Alzheimer-type dementia.

Clinical, neuropsychological and neuropsychophysiological data (Q-EEG, ERPs and CNV/RT activity) were obtained from 24 patients who had more or less severe presenile primary cognitive decline without depression, and compared with similar data from 10 age-matched healthy volunteers (mean age, 59.4 years). All of the patients (15 M and 9 F; mean age 59.6 years) were selected according to the DSM III-R, ICD-10 and NINCDS-ADRDA criteria and underwent CT and MRI scanning, in addition to a standard clinical examination, a battery of psychometric tests, spectral EEG, and bit-mapped CNV complex and RT to S2 analyses. Twelve of the 24 patients presented an initial presenile idiopathic cognitive decline (PICD) but did not wholly fulfil the clinical and neuropsychological criteria for primary dementia or for a diagnosis of probable AD; the remaining 12 patients showed characteristic clinical signs and symptoms of a very probable early stage of presenile Alzheimer-type dementia (PAD). ANOVA, correlational and discriminant analyses of the neuropsychological test scores, and the neurophysiological and RT to S2 data revealed 22 highest-ranked between-group discriminant factors (all with a significance level of p < 0.01). The conclusive discriminant analysis retained 13 of these factors as final canonical functions, and these showed a 97% grouping accuracy (33 of the 34 subjects examined); the same percentage of correct classifications was also achieved using only the 15 best indicators in the group of CNV/RT findings. Using both of these sets of highest-ranked discriminators, all of the normal subjects and all of the PAD patients were correctly classified; only 1 PICD patient was misclassified as normal when the first group of 13 factors was used, and another PICD patient was misclassified as PAD using the second group of 15 factors. Our findings suggest that, providing they are correctly performed and interpreted, these non-invasive techniques may be an important tool for identifying incipient stages of presenile Alzheimer-type dementia.

Is there a role for adjuvant immunochemotherapy after radical nephrectomy in pT2-3N0M0 renal cell carcinoma?

Five-year overall survival after radical surgery in N0M0 renal cell carcinoma varies from 45-80% in pT2 to 35-50% in pT3 categories. In view of the alpha interferon and vinblastine combination which has shown some activity in advanced disease with increasing efficacy in limited metastatic invasion, we decided to explore the theoretical advantage of adjuvant chemo-immunotherapy in radically resected stage II, III renal cell carcinoma. A single-institution phase II study was undertaken to evaluate the efficacy and tolerability of alpha 2a-interferon (alpha 2a-INF) in combination with vinblastine in 30 patients with pT2-T3 N0M0 renal cell carcinoma (RCC). Thirty-two patients who received only radical nephrectomy and extended lymphadenectomy were analyzed and results were compared with the first group. Twenty-three of 30 (76.6%) patients in the first group are alive with no evidence of disease. The median follow-up for the 23 patients still alive was 67 months (range 60 to 72). Metastases were documented in 5 patients (16.6%) with a median interval to progression of 24 months. Four of them (13.6%) died of tumor. In the control group, 16 out of 32 patients (50%) are still alive, with a median follow-up for the patients still alive of 62 months (range 60 to 68). Fifteen patients developed distant metastases and 2 of them had a local recurrence. All of them (46.8%) died of tumor. Median progression interval was 24 months. After stratification by pathological grade, site, laterality and number of nodes found at lymphadenectomy there were no statistical differences in risk of progression or death in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)