PubMed Health⌕ Search

Biomedical subjects

M G Bruzzone

Publications and source records attributed to M G Bruzzone.

At least 19 recordsLinked to original sources
PubMed2007

Bio-image warehouse system: concept and implementation of a diagnosis-based data warehouse for advanced imaging modalities in neuroradiology.

Advanced neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), chemical shift spectroscopy imaging (CSI), diffusion tensor imaging (DTI), and perfusion-weighted imaging (PWI) create novel challenges in terms of data storage and management: huge amounts of raw data are generated, the results of analysis may depend on the software and settings that have been used, and most often intermediate files are inherently not compliant with the current DICOM (digital imaging and communication in medicine) standard, as they contain multidimensional complex and tensor arrays and various other types of data structures. A software architecture, referred to as Bio-Image Warehouse System (BIWS), which can be used alongside a radiology information system/picture archiving and communication system (RIS/PACS) system to store neuroimaging data for research purposes, is presented. The system architecture is conceived with the purpose of enabling to query by diagnosis according to a predefined two-layered classification taxonomy. The operational impact of the system and the time needed to get acquainted with the web-based interface and with the taxonomy are found to be limited. The development of modules enabling automated creation of statistical templates is proposed.

Diagnostic Imaging↗
PubMed2006

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice.

In recent years, the use of dendritic cells (DC), the most powerful antigen presenting cells, has been proposed for the creation of vaccines against gliomas. This approach has been demonstrated to be safe and non-toxic in phase I or I-II trials (2, 3). Immunotherapy plays a central role in the search for new treatments for glioblastoma multiforme (GBM). In particular, several phase I studies have been performed using DC pulsed by GBM proteins as a vaccine for patients with relapsing GBM. The studies demonstrated that DC vaccination is safe and may produce a significant increase in overall survival. As the first step in the preparation of appropriate conditions for a clinical evaluation in Italy, we have performed pre-clinical experiments on immune-competent mice injected intra-cerebrally with syngeneic GL261GBM cells and treated subcutaneously and intra-tumorally with DC loaded with a GL261 homogenate. These results show that vaccination with DC pulsed with a tumor lysate increases considerably survival in mice bearing intracranial glioblastomas and supports the development of DC-based clinical trials for patients with glioblastomas that do not respond to standard therapies.

Animals↗
PubMed2006

Molecular markers of gliomas: a clinical approach.

Over the last decade, the knowledge on the molecular genetic background of gliomas has dramatically increased. This information provides the basis for the molecular target therapies and molecular tests serve to complement the subjective nature of histopathologic criteria and add useful data regarding response to treatments and prognosis. In particular, the use of loss of heterozygosity (LOH) and methylation specific polymerase chain reaction (PCR) (MSP) based testing of gliomas is already in place and used clinically in several centers. This paper provides a brief overview of these molecular genetic aberrations and discusses the clinical utility, as well as the advantages and disadvantages of such approach. Newly developed molecular techniques, such as LOH testing, fluorescence in situ hybridization (FISH), DNA sequencing and MSP, are currently being employed in assessment of gliomas in some laboratories. However, the clinical use of some markers and the context in which the information obtained should be used are still not entirely understood. Therefore, this paper will focus on validation and implementation of molecular testing in gliomas, with emphasis on LOH on chromosomes 1p, 19q, 17p and 10q and O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status.

Biomarkers, Tumor↗
PubMed2004

Neuroradiological features of vertigo.

The diagnostic pathway in a patient with vertigo starts with the accurate evaluation of medical history followed by a general physical and neurological examination. This step can often lead to the identification of the correct cause of the disease or, at least, to a distinction between peripheral and central vertigo. Neuroradiological investigations have to be considered as elective diagnostic procedures and include: computed tomography (CT), magnetic resonance (MR), MR angiography (MRA), angiography. For the diagnosis of peripheral vertigo, benign paroxysmal positional vertigo, labyrinthitis, Meniere disease, perilymphatic fistula, local trauma, toxic labyrinthitis, acute otitis media and chronic middle ear effusion,the role of imaging techniques is controversial. CT and MR are performed to rule out other pathologies and to confirm the diagnosis. Increased resolution and application of special MR sequences enhancing the intralabyrinthine fluids have enabled more detailed analysis of labyrinthine structures and pathology. Both T2 and T1 contrast sequences are necessary. A high resolution CT study is required when otitis media is suspected and in the follow-up of post-traumatic vertigo. The causes of central vertigo are numerous and include: vertebro-basilar circulation vascular events, multiple sclerosis (MS), migraine-associated vertigo, cerebellar and brainstem tumors, CNS infections. Among them cerebrovascular ischemia and multiple sclerosis are the most frequent. In these situations imaging studies become mandatory. CT can diagnose most cerebellar hemorrhages and some cerebellar and brainstem acute ischemia, enhanced MR has proved to be the most sensitive tool to detect posterior fossa lesion. Diffusion-weighted MR can reveal acute ischemic changes before routine MR. There has been evidence that MR angiography, providing angiogram-like images of the intracranial vessels may sometimes avoid invasive angiography. MRA resolution is not as good as traditional angiography and may also be compromised by movements and other artifacts. Selective angiography of the posterior circulation is often indicated for therapeutic decisions.

Brain↗
PubMed2000

Neuropsychological testing may predict early progression of asymptomatic adrenoleukodystrophy.

OBJECTIVES: To investigate the correlation between neuropsychological and MRI findings in children with the childhood cerebral (CCALD) and asymptomatic forms of X-linked adrenoleukodystrophy (ALD) and to identify early cognitive markers that may predict disease progression in asymptomatic children with ALD. BACKGROUND: The few published neuropsychological studies on CCALD suggest a correlation between the pattern of cognitive deficit and lesion site; however, neuropsychological performance in asymptomatic children with ALD has not been investigated. METHODS: The authors assessed cognitive function and cerebral MRI findings in seven CCALD and eight asymptomatic ALD children. RESULTS: The CCALD children's cognitive skills were severely compromised, especially Wechsler and executive functions. Visual perception, short-term memory, and language were generally preserved, except that naming was severely impaired. All had extensive posterior white matter deterioration. The asymptomatic children had relatively intact neuropsychological performance, but their verbal fluency was compromised and naming severely impaired. All except one had mild white matter alterations. For all the children, the majority of neuropsychological test performance correlated significantly with extent of white matter lesions. CONCLUSIONS: The pattern of cognitive deterioration in children with CCALD and the significant correlation of neuropsychological test performance with extent of white matter lesions indicate a white matter dementia similar to that observed in adults with demyelinating diseases. The deficits found in asymptomatic children, despite their normal intelligence, suggest that careful neuropsychological investigation can identify early signs of malfunction. These may be markers of disease progression useful for selecting children for bone marrow transplant, although this will require confirmation by prospective longitudinal studies.

Adolescent↗
PubMed2000

Gene therapy of experimental brain tumors using neural progenitor cells.

Glioblastomas, the most frequent and malignant of primary brain tumors, have a very poor prognosis. Gene therapy of glioblastomas is limited by the short survival of viral vectors and by their difficulty in reaching glioblastoma cells infiltrating the brain parenchyma. Neural stem/progenitor cells can be engineered to produce therapeutic molecules and have the potential to overcome these limitations because they may travel along the white matter, like neoplastic cells, and engraft stably into the brain. Retrovirus-mediated transfer of the gene for interleukin-4 is an effective treatment for rat brain glioblastomas. Here, we transferred the gene for interleukin-4 into C57BL6J mouse primary neural progenitor cells and injected those cells into established syngeneic brain glioblastomas. This led to the survival of most tumor-bearing mice. We obtained similar results by implanting immortalized neural progenitor cells derived from Sprague-Dawley rats into C6 glioblastomas. We also documented by magnetic resonance imaging the progressive disappearance of large tumors, and detected 5-bromodeoxyuridine-labeled progenitor cells several weeks after the injection. These findings support a new approach for gene therapy of brain tumors, based on the grafting of neural stem cells producing therapeutic molecules.

Animals↗
PubMed1999

Eradication of rat malignant gliomas by retroviral-mediated, in vivo delivery of the interleukin 4 gene.

Overexpression of interleukin 4 (IL-4) can impair the tumorigenicity of glioma cells, but direct evidence of its antitumor efficacy after in vivo gene transfer into malignant gliomas has not been provided. To test this, we first injected into the brain of Sprague Dawley rats a 1:1 mixture of C6 rat glioblastoma cells and psi2.L4SN20 or E86.L4SN50 retroviral producer cells (RPCs), secreting 20 and 50 ng of IL-4/5 x 10(5) cells/48 h, respectively. Twenty-seven and 56% of rats receiving injections with these low- or medium-level IL-4 RPCs, respectively, survived tumor injection, whereas control rats died in about 1 month. E86.L4SN50 RPCs coinjected with 9L gliosarcoma cells into syngeneic Fischer 344 rats yielded similar results. A novel IL-4 RPC clone expressing higher levels of IL-4, E86.L4SN200, coinjected with 9L cells increased to 75% the fraction of long-term survivors and induced tumor regression in 50% of rats when injected into established 9L gliosarcomas. Cured rats developed an immunological memory because they rejected a challenge of wild-type 9L cells into the contralateral hemisphere. Magnetic resonance imaging was used to monitor 9L and C6 gliomas and gave direct evidence for tumor rejection in treated rats. Immunohistology showed inflammatory infiltrates in IL-4-treated tumors in which CD8+ T lymphocytes were more abundant, although CD4+ T lymphocytes, B lymphocytes, and macrophages were also present. Overall, these findings suggest that IL-4 gene transfer is a new, promising approach for treating malignant gliomas.

Animals↗
PubMed1999

Infantile neuroaxonal dystrophy: neuroradiological studies in 11 patients.

We report the imaging findings in 11 patients with infantile neuroaxonal dystrophy. Ten patients underwent 15 MRI examinations; one patient had only CT. Of the ten patients who underwent MRI, eight had cerebellar atrophy and mildly increased signal from the cerebellar cortex on T2-weighted images. With T2 weighting there was slightly increased signal from the dentate nuclei in two patients and from the posterior periventricular white matter in three. We saw four patients with a thin optic chiasm. The only two brothers in the series had markedly low signal from the globus pallidus and substantia nigra on 1.5 T T2-weighted images, as seen in Hallervorden-Spatz disease (HSD). Abnormalities of the globus pallidus may be related to a protracted course of the disease. However, an overlap with HSD should be considered.

Brain↗
PubMed1997

Limited efficacy of the HSV-TK/GCV system for gene therapy of malignant gliomas and perspectives for the combined transduction of the interleukin-4 gene.

The growth of U-87 or C6 gliomas co-implanted in nude mice with retroviral producer cells (VPC) expressing the herpes simplex virus-thymidine kinase (HSV-tk) gene is only partially impaired by treatment with ganciclovir (GCV). The effect of GCV is even less evident when C6 and VPC are co-implanted into the rat brain. Furthermore, tumors from C6 cells carrying the HSV-tk gene are not eradicated by GCV, although they remain sensitive to GCV when replated in vitro. These limits of the HSV-tk/GCV system in glioma gene therapy may be due to insufficient gene transfer and/or insufficient delivery of GCV to glioma cells. Combination of HSV-tk and one or more cytokines may improve the antitumor efficacy. Among cytokines, interleukin-4 (IL-4) has already been shown to be active against gliomas. In nude mice, GCV treatment inhibited tumor growth more effectively after co-injection of C6 cells with a mixture of VPC transducing IL-4 and HSV-tk genes than after co-injection with either IL-4 or HSV-tk VPC only. In immunocompetent Sprague-Dawley rats, co-injection of IL-4 VPC and C6 cells was also effective in inhibiting the growth of C6 brain tumors, 38% of the animals surviving for at least 2 months. Furthermore, increased and prolonged antitumor efficacy was obtained by transducing both IL-4 and HSV-tk genes.

Animals↗
PubMed1997

Gene transfer of suicide genes for the treatment of malignant gliomas: efficacy, limitations, and perspectives for a combined immunotherapy.

The potential of gene therapy strategies for malignant gliomas that are based on retroviral-mediated transfer of a "suicide gene" such as Herpes Simplex Virus-thymidine kinase HSV-tk and subsequent treatment by a prodrug (ganciclovir, for example), has been emphasized by the promising results obtained by several groups. However, further experimental data as well as preliminary clinical results indicate that the low efficiency of retroviral-mediated gene transfer in vivo as well as difficulties for the diffusion of the prodrug inside the tumour mass can limit the efficacy of this form of gene therapy. To achieve a more effective limitation of tumour growth other approaches may be combined with the "suicide gene" strategy and the enhancement of the immunological response to the tumour by cytokine gene transfer is prominent among these approaches. The authors' experiments in nude mice confirm the antineoplastic role of IL-4 and encourage testing the effects of the simultaneous transfer of IL-4 and HSV-tk genes in immunocompetent animals.

Animals↗
PubMed1997

Clinical applications of an ATM/Ethernet network in departments of neuroradiology and radiotherapy.

An integrated system for the multimedia management of images and clinical information has been developed at the Isituto Nazionale Neurologico C. Besta in Milan. The Institute physicians have the daily need of consulting images coming from various modalities. The high volume of archived material and the need of retrieving and displaying new and past images and clinical information has motivated the development of a Picture Archiving and Communication System (PACS) for the automatic management of images and clinical data, related not only to the Radiology Department, but also to the Radiotherapy Department for 3D virtual simulation, to remote teleconsulting, and in the following to all the wards, ambulatories and labs.

Computer Communication Networks↗
PubMed1996

MRI features of cerebral lesions and cognitive functions in preterm spastic diplegic children.

The aim of this study is to further clarify the relation between the pattern of cognitive impairment in spastic diplegic children born preterm and MRI features of cerebral lesions. The cognitive profile by Wechsler Scale of a sample of 30 children aged 6 years, 8 months to 14 years, 7 months was assessed, and the correlations between the Full Scale, Verbal, and Performance IQ and periventricular leukomalacia features on MRI were investigated. A significant difference was observed between the mean Verbal and Performance IQ, indicating a specific failure in the visuoperceptual functions of spastic diplegic children born preterm. Periventricular leukomalacia was detected in all children. The severity of ventricular dilatation, the degree and extent of white matter reduction, optic radiation involvement, and the thinning of the posterior corpus callosum correlated significantly with the Full Scale and Performance IQ: no correlation was observed between the Verbal IQ and any of the MRI features analyzed. In spastic diplegic children, an MRI examination between the ages of 1 and 2 years may be helpful in predicting a specific neuropsychological pattern of dysfunction and in defining an early intervention program.

Adolescent↗
PubMed1994

Primary antiphospholipid syndrome (PAPS) and isolated partial seizures in adolescence. A case report.

The case of a young male patient presenting isolated clustered partial seizures is reported. Despite the normality of the neurological features, as well as of ictal and interictal EEG, the MRI (performed three days after the symptoms) disclosed bilateral signal alterations in the parietal cortical region. These abnormalities disappeared at the MRI control examination performed one month later. The finding of positive anticardiolipine antibodies made possible the diagnosis of partial epileptic seizures symptomatic of a vascular disorder ascribed to a Primary antiphospholipid Syndrome (PAPS).

Adolescent↗
PubMed1993

Hemidystonia symptomatic of primary antiphospholipid syndrome in childhood.

We report three children with hemidystonia in whom anti-cardiolipin (aCL) antibodies were demonstrated. Systemic lupus erythematosus was excluded on the basis of both clinical and serological criteria, and the diagnosis of primary antiphospholipid syndrome (PAPS) was made. In two cases, aCL antibodies could be causally related to a presumed immune-mediated thrombotic event involving the basal ganglia as shown by magnetic resonance imaging (MRI). In the remaining patient the finding of white matter alteration on NMR might be due to cross-reactivity of anti-phospholipid (aPL) antibodies with cerebral phospholipids, resulting in demyelination. We suggest that PAPS must always be considered when isolated or recurrent focal cerebral ischaemia, and particularly hemidystonia, occur in childhood.

Antibodies, Anticardiolipin↗
PubMed1993

Clinical features and MR imaging in children with repaired myelomeningocele.

The aim of the study is to define the role of associated malformations in the clinical evolution of children affected by myelomeningocele. MRI investigation of the spinal cord was carried out on 25 patients between the age of 7.3 and 18.10 with MMC repaired and followed up for at least 7 years. The relation between associated malformations demonstrated by MRI and clinical trend was analysed. The results are the following: 1) presence of asymptomatic tethered cord in all cases; 2) high frequency (92%) of Chiari malformation; 3) presence of syringomyelia in 20% of patients, symptomatic in 1; 4) presence of ventricular enlargement in 72% of cases without increased intracranial pressure syndrome. For a better therapeutic approach prospective MRI studies are needed in order to follow up associated malformations.

Adolescent↗