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F Fazio

Publications and source records attributed to F Fazio.

At least 91 records · Page 5Linked to original sources

18-FDG positron emission tomography in the evaluation of malignant pleural diseases - a pilot study.

OBJECTIVE: The diagnostic approach to pleural diseases may be difficult. The CT scan, which is the current diagnostic technique, has limited accuracy both in the differentiation between benign and malignant pleural diseases and in the diagnosis of primary and metastatic pleural neoplasms. Invasive procedures, such as thoracoscopy, are therefore frequently required to complete the diagnostic approach. The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies, which still need to be fully validated. There is, therefore, a need for new diagnostic techniques that can lead to a definite diagnosis and a satisfactory evaluation of the response to treatment. Encouraging results have been reported with the F-18-labeled analogue of 2-deoxyglucose (18-FDG) positron emission tomography (PET) in the evaluation of chest tumors such as lung cancer. The aim of this study was to evaluate the role of 18-FDG PET in the diagnostic assessment of pleural diseases. METHODS: Patients with CT scan evidence of pleural thickening, or fluid, entered a study to evaluate the accuracy of 18-FDG PET in diagnosing pleural diseases. Image analysis was performed both with visual interpretation and using a semiquantitative method, standardized uptake values (SUV), on coronal, sagittal and axial reconstructions. The results of PET imaging were compared to histological data. PET was also performed before and after treatment in patients who underwent chemotherapy to evaluate the accuracy of this technique in the assessment of the response. RESULTS: Fourteen patients entered the study. Histology demonstrated a malignant pleural disease in 13 patients; malignant pleural mesothelioma in ten patients, adenocarcinoma in two and liposarcoma in one. Benign pleural disease was diagnosed in the remaining patient. PET assessment demonstrated significant 18-FDG uptake in 12 of the 13 patients with a malignant disease, also revealing distant metastases in two of them. A false-negative result was observed in a patient with an epithelial mesothelioma. The overall accuracy was 92%. A benign pleural disease without significant uptake was correctly diagnosed in another patient. An aspecific uptake was observed in two patients who had undergone pleurectomy and intrapleural chemotherapy. A decreased tracer uptake was observed after chemotherapy in four patients. CONCLUSIONS: These preliminary results demonstrate that 18-FDG PET may have a great potential, both in the differential diagnosis of pleural diseases and in the evaluation of the response to treatment. At present, however, histological thoracoscopic diagnosis remains mandatory before planning treatment. Further studies in larger groups of patients are needed to draw definite conclusions on the role of PET in the assessment of pleural diseases.

Adenocarcinoma↗

A cultural effect on brain function.

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.

Adult↗

Diagnosis of persistent ovarian carcinoma with three-step immunoscintigraphy.

The diagnosis of recurrent ovarian carcinoma is usually determined at surgical re-exploration since the main non-invasive diagnostic tests have low accuracy. It would be desirable to have a high accuracy non-invasive diagnostic procedure. With this aim, we have assessed the utility of three-step immunoscintigraphy. Thirty patients were intravenously injected with biotinylated monoclonal antibodies MOv18 and B72.3, followed by avidin-streptavidin injection and finally by 111In-biotin. Tumour recurrences were imaged 2 h post radioactivity injection. All patients underwent surgical re-exploration 3-4 days after immunoscintigraphy; the presence of tumour in the area of immunoscintigraphic uptake was evaluated in the biopsied material. Twenty-one patients studied were true-positive, five were true-negative, four were false-positive and none was false-negative. The diagnostic accuracy, positive predictive value and negative predictive value were 87%, 84% and 100% respectively. If these findings are confirmed in a larger number of patients, we expect immunoscintigraphy to be introduced as a cost-effective procedure in the follow-up of patients who have received surgery for ovarian carcinoma, since it promises to reliably identify patients who do not require surgical re-exploration, and guide biopsies when they are indicated.

Adult↗

Molecular analysis of the N-acetyltransferase 1 gene (NAT1*) using polymerase chain reaction-restriction fragment-single strand conformation polymorphism assay.

One major interest to analyse the extent of N-acetyltransferase 1 (NAT1*) allelic variation in the human population stems to a great extent from the possible association of interindividual differences in the metabolism of aromatic amines with certain chemically induced diseases, including cancer. Considering the increasing number of mutations in the NAT1 gene that are detected, NAT1* genotyping using conventional polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) or allele-specific amplification assays has become complicated. We developed a rapid and powerful strategy allowing the full characterization of NAT1* alleles. This method, based on single-strand conformation polymorphism analysis of a unique PCR product encompassing the entire intronless NAT1*-coding region along with additional flanking segments in the 5' and 3' untranslated regions, was then applied to DNA samples from 270 individuals. Nine NAT1* allelic variants, including two novel (NAT1*28 and NAT1*29), and 15 different genotypes were identified. This approach could be advantageously used in epidemiological studies to provide more definite data on suspected associations between NAT1* genotype and certain pathological processes.

Alleles↗

Reversal of left ventricular diastolic dysfunction after kidney-pancreas transplantation in type 1 diabetic uremic patients.

OBJECTIVE: Diastolic function is frequently impaired in diabetic patients. Our aim was to evaluate the effects of glycometabolic control achieved by pancreas transplantation on left ventricular function in uremic type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Left ventricular systolic and diastolic functions were evaluated using radionuclide ventriculography in 42 kidney-pancreas transplant patients and 26 kidney-alone recipients who had similar clinical characteristics before transplantation. Patients were grouped according to 6, 24, and 48 months of follow-up. Control subjects consisted of 20 type 1 diabetic patients. RESULTS: The left ventricular ejection fraction was normal in all of the patients. However, kidney-pancreas transplant patients with 4 years of graft function had a higher ejection fraction (75.7 +/- 1.8%) than kidney-alone patients with 4 years of graft function (65.3 +/- 2.8%, P = 0.02) and type 1 diabetic patients (61.3 +/- 3.7%, P = 0.004). In patients with 4 years of graft function, normal diastolic parameters were evident in kidney-pancreas but not in kidney-alone or in type 1 diabetic patients (peak filling rate: 4.46 +/- 0.15 end diastolic volume (EDV)/s in kidney-pancreas patients vs. 2.73 +/- 0.24 EDV/s [P < 0.01] and 3.39 +/- 0.30 EDV/s [P < 0.01] in kidney-alone and type 1 diabetic patients, respectively; time-to-peak filling rate: 141.9 +/- 7.8 ms in kidney-alone patients vs. 209.4 +/- 13.5 ms in kidney-alone patients [P < 0.01]; peak filling rate/peak ejection rate ratio: 1.10 +/- 0.04 in kidney-pancreas patients vs. 0.81 +/- 0.08 in kidney-alone patients [P < 0.01]). A significant reduction in diastolic dysfunction rate was observed only in kidney-pancreas patients. CONCLUSIONS: Kidney-pancreas transplantation results in complete insulin independence, a better glycometabolic pattern and blood pressure control, an improvement of left ventricular function, and a reversal of diastolic dysfunction.

Adult↗

Reduced cerebral blood flow and impaired visual-spatial function in proximal myotonic myopathy.

OBJECTIVE: To compare brain involvement in myotonic dystrophy (DM) with that of proximal myotonic myopathy (PROMM). BACKGROUND: PROMM is a multisystem disease with many features in common with DM. METHODS: Twenty patients with DM (CTGF[500-700), 20 patients with PROMM, and 20 normal control subjects were studied. Neuropsychological testing was performed in 12 patients with PROMM and in 18 patients with DM; brain MRI was performed in 17 of 20 PROMM patients and 15 of 20 DM patients. Ten patients with PROMM and 11 patients with DM were subjected to H2(15)O PET. RESULTS: Two-thirds of the patients with PROMM and one-half of those with DM were impaired on visual-spatial recall, whereas one-third of the patients with PROMM and less than half of those with DM showed an impairment in visual-spatial construction. Brain MRI was normal, or showed only nonspecific white matter abnormalities in both PROMM and DM patients. PET studies in PROMM patients showed a bilateral decrease in regional cerebral blood flow (rCBF) of the orbitofrontal and medial frontal cortex, whereas DM patients had more widespread hypoperfusion that extended to the dorsolateral frontal cortex and subcortical regions. CONCLUSIONS: Impaired visual-spatial function may be present in proximal myotonic myopathy. This correlates best with a reduction in regional cerebral blood flow observed in H2(15)O PET brain scans rather than with specific structural abnormalities observed on brain MRI.

Adolescent↗

Impaired movement control in Alzheimer's disease.

Movement accuracy in normal subjects depends on feedforward commands based on representation in memory of spatial and biomechanical features. Here we ask whether memory deficits in Alzheimer's disease (AD) interfere with movement planning and execution. Nine AD patients and nine age-matched controls moved a cursor to targets without seeing their limb. Starting and target positions were always visible on a screen, while, during movement, cursor position was either visible or blanked. Patients' paths showed discontinuous segments and prolonged movement time; movement inaccuracy, which increased without visual feedback, correlated significantly with scores of disease severity, working memory and attention.

Alzheimer Disease↗

Rapid assessment of regional cerebral metabolic abnormalities in single subjects with quantitative and nonquantitative [18F]FDG PET: A clinical validation of statistical parametric mapping.

The [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has not the wide clinical application that one might expect, partly because of its high cost and the complexity of the quantification procedure, but also because of reporting techniques based on region of interest (ROI) analysis, which are time-consuming and not fully objective. In this paper we report a clinical validation of statistical parametric mapping (SPM) using rCMRglc (quantitative) and radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10-min noninteractive voxel-based SPM analysis on a standard workstation enables objective assessment, including localization in stereotactic space, of regional glucose consumption abnormalities, whose reliability can be assessed on statistical and clinical grounds. Clinical validity was established using a small series of patients with degenerative or developmental disorders, including probable Alzheimer's disease, progressive aphasia, multiple sclerosis, developmental specific language impairment, and epilepsy. Analysis of quantitative and nonquantitative data showed the same pattern of results, suggesting that, for clinical purposes, quantitation and invasive arterial cannulation can be avoided. This should facilitate a wider application of the technique and the extension of SPM clinical analysis to H215O PET or high resolution SPECT perfusion studies.

Adolescent↗

Pathways of interhemispheric transfer in normals and in a split-brain subject. A positron emission tomography study.

We studied with PET the intra- and interhemispheric pathways subserving a simple, speeded-up visuomotor task. Six normal subjects and one patient with a complete section of the corpus callosum (M.E.) underwent regional cerebral blood flow (rCBF) measurements under conditions of lateralized tachistoscopic visual presentations in a simple manual reaction time paradigm. Confirming previous behavioural findings, we found that on average crossed hand and/or hemifield conditions, i.e. those requiring an interhemispheric transfer of information, yielded a longer RT than uncrossed conditions. This difference (0.7 ms) was dramatically larger (45.6 ms) in the callosum-sectioned patient M.E. In normal subjects the cortical areas selectively activated in uncrossed and crossed conditions were different. In the former condition, most activation foci were anterior to the ventral anterior commissure (VAC) plane, whereas in the latter there was a prevalent parietal and occipital activation. This shows that a simple model in which the cortical visuo-motor pathways are similar in the intra- and the interhemispheric condition, with an extra callosal route for the latter, is too simplistic. Furthermore, these results suggest that the bulk of visuomotor interhemispheric transfer takes place through the widespread callosal fibres interconnecting the parietal cortices of the two hemispheres. The pattern of activation in the two crossing conditions was markedly different in M.E., in whom interhemispheric transfer might take place via his intact anterior commissure or subcortical commissures.

Adult↗

An automatic classification technique for attenuation correction in positron emission tomography.

In this paper a clustering technique is proposed for attenuation correction (AC) in positron emission tomography (PET). The method is unsupervised and adaptive with respect to counting statistics in the transmission (TR) images. The technique allows the classification of pre- or post-injection TR images into main tissue components in terms of attenuation coefficients. The classified TR images are then forward projected to generate new TR sinograms to be used for AC in the reconstruction of the corresponding emission (EM) data. The technique has been tested on phantoms and clinical data of brain, heart and whole-body PET studies. The method allows: (a) reduction of noise propagation from TR into EM images, (b) reduction of TR scanning to a few minutes (3 min) with maintenance of the quantitative accuracy (within 6%) of longer acquisition scans (15-20 min), (c) reduction of the radiation dose to the patient, (d) performance of quantitative whole-body studies.

Brain↗

Word and picture matching: a PET study of semantic category effects.

We report two positron emission tomography (PET) studies of cerebral activation during picture and word matching tasks, in which we compared directly the processing of stimuli belonging to different semantic categories (animate and inanimate) in the visual (pictures) and verbal (words) modality. In the first experiment, brain activation was measured in eleven healthy adults during a same/different matching task for textures, meaningless shapes and pictures of animals and artefacts (tools). Activations for meaningless shapes when compared to visual texture discrimination were localized in the left occipital and inferior temporal cortex. Animal picture identification, either in the comparison with meaningless shapes and in the direct comparison with non-living pictures, involved primarily activation of occipital regions, namely the lingual gyrus bilaterally and the left fusiform gyrus. For artefact picture identification, in the same comparison with meaningless shape-baseline and in the direct comparison with living pictures, all activations were left hemispheric, through the dorsolateral frontal (Ba 44/6 and 45) and temporal (Ba 21, 20) cortex. In the second experiment, brain activation was measured in eight healthy adults during a same/different matching task for visually presented words referring to animals and manipulable objects (tools); the baseline was a pseudoword discrimination task. When compared with the tool condition, the animal condition activated posterior left hemispheric areas, namely the fusiform (Ba 37) and the inferior occipital gyrus (Ba 18). The right superior parietal lobule (Ba 7) and the left thalamus were also activated. The reverse comparison (tools vs animals) showed left hemispheric activations in the middle temporal gyrus (Ba 21) and precuneus (Ba 7), as well as bilateral activation in the occipital regions. These results are compatible with different brain networks subserving the identification of living and non-living entities; in particular, they indicate a crucial role of the left fusiform gyrus in the processing of animate entities and of the left middle temporal gyrus for tools, both from words and pictures. The activation of other areas, such as the dorsolateral frontal cortex, appears to be specific for the semantic access of tools only from pictures.

Adult↗

Effects of dopamine on the in vivo binding of dopamine D2 receptor radioligands in rat striatum.

The effects of moderate changes in extracellular dopamine concentrations on the in vivo binding of specific dopaminergic D2 radioligands with different affinities and kinetics were investigated in rats. Either [125I]NCQ298 (Kd = 19 pM), or [25I]iodolisuride (Kd = 0.27 nM) or [3H]raclopride (Kd = 1.5 nM) were administered intravenously (IV) to animals 1 h after the intraperitoneal (IP) injection of either alpha-methyl-p-tyrosine (AMPT) (250 mg/kg) or nomifensine (15 mg/kg), or saline. The kinetics of radioactivity concentration in the striatum, cerebellum, and plasma were measured for up to 4 h after [125I]NCQ298 or [125I]iodolisuride injection and up to 1.5 h after [3H]raclopride injection. For each tracer, the striatum-to-cerebellum radioactivity concentration ratios (S/C) and the binding potential (BP), calculated as the association to dissociation binding rate constant ratios (k3/k4), were assessed and related to the changes in extracellular dopamine concentration induced by drug treatments. Results show that S/C and BP of [3H]raclopride were significantly diminished by pretreatment with nomifensine, a drug that increases extracellular dopamine concentration. Nomifensine pretreatment induced no changes in the in vivo binding indexes of the high affinity [125I]NCQ298 and a slight but not significant decrease of the binding indexes of 125I]iodolisuride. Treatment with AMPT, which induced a 40% reduction in dopamine concentration, did not change [125I]NCQ298 binding indexes but slightly increased those of [3H]raclopride and [125I]iodolisuride. In conclusion, the change of dopamine concentration induces modification of radiotracer kinetics. Thus, the combined use of tracers with high and low affinities could allow us to obtain information both on receptor density and neurotransmitter release in vivo. However, as indicated by the [3H]raclopride study with AMPT, small changes in the concentration of intrasynaptic dopamine cannot be easily detected.

3,4-Dihydroxyphenylacetic Acid↗

The neural correlates of verb and noun processing. A PET study.

The hypothesis that categorical information, distinguishing among word classes, such as nouns, verbs, etc., is an organizational principle of lexical knowledge in the brain, is supported by the observation of aphasic subjects who are selectively impaired in the processing of nouns and verbs. The study of lesion location in these patients has suggested that the left temporal lobe plays a crucial role in processing nouns, while the left frontal lobe is necessary for verbs. To delineate the brain areas involved in the processing of different word classes, we used PET to measure regional cerebral activity during tasks requiring reading of concrete and abstract nouns and verbs for lexical decision. These tasks activated an extensive network of brain areas, mostly in the left frontal and temporal cortex, which represents the neural correlate of single word processing. Some left hemispheric areas, including the dorsolateral frontal and lateral temporal cortex, were activated only by verbs, while there were no brain areas more active in response to nouns. Furthermore, the comparison of abstract and concrete words indicated that abstract word processing was associated with selective activations (right temporal pole and amygdala, bilateral inferior frontal cortex), while no brain areas were more active in response to concrete words. There were no significant interaction effects between word class and concreteness. Taken together, these findings are compatible with the view that lexical-semantic processing of words is mediated by an extensive, predominantly left hemispheric network of brain structures. Additional brain activations appear to be related to specific semantic content, or, in the case of verbs, may be associated with the automatic access of syntactic information.

Adult↗

Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations.

OBJECTIVE: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations. METHODS: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never-NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)). RESULTS: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never-NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory. CONCLUSIONS: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.

Adult↗

Characterization of a variable number tandem repeat region in the thiopurine S-methyltransferase gene promoter.

Characterization of the genetic polymorphism of thiopurine S-methyltransferase enzyme (TPMT; EC 2.1.1.67) is required because of its clinical importance for patients exposed to thiopurine drugs. A number of point mutations have already been characterized in exons and introns of the TPMT gene. Here we report the identification of a polymorphic locus within the promoter region of the gene. This polymorphism was detected by polymerase chain reaction - single strand conformation polymorphism analysis of DNA samples from 54 unrelated European individuals. A total of five alleles with length variations were distinguished through the 5'-flanking region involved in the TPMT gene expression. Sequence analysis revealed that these variations were due to a variable number of tandem repeats (VNTR), ranging from four to eight repeats. Each repeat consists of 17 or 18 bp units and contains putative binding sites for transcription factors. The most frequent alleles harbour four or five tandem repeats, a heterozygosity rate of 0.44 was calculated, and a stable Mendelian inheritance of alleles was demonstrated. Analysis of the effect of each VNTR allele on promoter activity of a reporter gene was further performed in various cell lines by transient transfection assay. A modulatory effect of VNTR alleles was observed in vitro, but the repeat polymorphism did not display a significative role in TPMT gene regulation in vivo. Further studies need to be carried out to support the hypothesis that VNTR may contribute to the large interindividual variations of TPMT activity.

Animals↗