Biomedical subjects
Publications and source records attributed to A Pupi.
Germ cell tumor is the most common malignancy in young men. The cure rate of these patients has tremendously increased in the cisplatin era, and recent results have indicated that the management of patients with GCT is still improving. The use of FDG-PET in the management of patients with GCT has been recently investigated. This report attempts to comprehensively review new advances and delineate the potential applications of FDG-PET in GCT.
BACKGROUND: Clinically apparent Alzheimer's disease (AD) is thought to result when brain tissue damage exceeds a critical threshold of "brain reserve", a process possibly accelerated by the apolipoprotein E (ApoE) E4 allele. The interaction between onset age and ApoE genotype was investigated to assess whether early disease onset (<65 years) in patients carrying the E4 allele is associated with greater cerebral metabolic (regional cerebral metabolic rate of glucose utilisation, rCMRgl) reduction. METHODS: AD patients, divided into early (EOAD; 27 patients) and late onset (LOAD; 65 patients) groups, both groups balanced as to the number of E4 carriers (E4+) and non-carriers (E4-), and matched controls (NC; 35 cases) underwent (18)F-FDG PET ([(18)F]fluorodeoxyglucose positron emission tomography) scanning. SPM'99 software was used to compare AD patients to NC and to perform a two way ANOVA with onset age and ApoE genotype as grouping factors. Results were considered significant at p<0.001, uncorrected. RESULTS: AD patients demonstrated rCMRgl reductions compared to NC, with rCMRgl lower in association cortex and relatively higher in limbic areas in EOAD compared to LOAD subjects. rCMRgl was lower in the anterior cingulate and frontal cortex for E4+ compared to E4- subjects. A significant onset age by ApoE interaction was detected in the hippocampi and basal frontal cortex, with EOAD E4+ subjects having the greatest rCMRgl reduction. CONCLUSIONS: The interactive effects of early onset age, possibly reflecting lower brain reserve, and ApoE E4 allele, possibly leading to greater tissue damage, lead to reduced tolerance to the pathophysiological effects of AD in key brain regions.
AIM: The aim of this study was three-fold: 1) to quantify [131I]-6beta-iodomethyl-norcholesterol ([131I]-NP-59) adrenal uptake trend in patients with incidentalomas, 2) to identify a specific uptake trend (TREND) capable of characterising pre-clinical Cushing syndrome (PC-CS) patients, 3) to assess the clinical availability of TREND as a prognostic factor of late clinical outcome in a cohort of patients with bilateral adrenal adenomas. METHODS: Fifty-seven consecutive patients were examined using three-head SPECT at 24, 48, 72 hours following intravenous injection of [131I ]-NP-59. On the basis of the absence or presence of hormonal abnormalities, the selected population was classified as GR1 or GR2, respectively. Adrenal glands were classified into 4 groups taking into account both the patient group (GR1, GR2) and the presence (+) or absence (-) of the adenoma (AD) on CT scan. Using ROI technique, adrenal-liver uptake ratio (A/L) was estimated bilaterally at 24, 48 and 72 hours. For each adrenal group, mean [131I]-NP-59 uptake trends were derived. RESULTS: TREND was significantly different between GR1/AD+ and GR2/AD+. Among GR2/AD+ patients, TREND correctly identified PC-CS with a global accuracy of 74%. Two patients with bilateral incidentaloma developed an overt CS. In both patients, TREND correctly identified the hyperfunctioning adrenal, thus permitting an effective sparing adrenalectomy. CONCLUSIONS: TREND seems to be a parameter which closely reflects adrenal physiological behaviour, especially in the case of bilateral adrenal involving. The possibility to quantify even contralateral adrenal uptake as standardised index provides additional useful information about normal adrenal parenchyma and, indirectly, about adenoma functional autonomy.
OBJECTIVES: To investigate whether the combination of fluoro-2-deoxy-d-glucose (FDG) PET measures with the APOE genotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHOD: After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in baseline regional glucose metabolic rate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (converters [n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [n = 16] vs noncarriers [E4-] [n = 21]) as grouping factors. Results were considered significant at p < 0.05, corrected for multiple comparisons. RESULTS: All converters showed reduced rCMRglc in the inferior parietal cortex (IPC) as compared with the nonconverters. Hypometabolism in AD-typical regions, that is, temporoparietal and posterior cingulate cortex, was found for the E4+ as compared with the E4- patients, with the E4+/converters (n = 5) having additional rCMRglc reductions within frontal areas, such as the anterior cingulate (ACC) and inferior frontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion to AD with 84% overall diagnostic accuracy (p = 0.003). Moreover, ACC and IFC rCMRglc improved prediction for the E4+ group, yielding 100% sensitivity, 90% specificity, and 94% accuracy (p < 0.0005), thus leading to an excellent discrimination. CONCLUSION: Fluoro-2-deoxy-d-glucose-PET measures may improve prediction of the conversion to Alzheimer disease, especially in combination with the APOE genotype.
OBJECTIVES: Declines in brain glucose metabolism have been described early in Alzheimer's disease (AD), and there is evidence that a genetic predisposition to AD contributes to accelerate this process. The epsilon 4 (e4) allele of the apolipoprotein E (ApoE) gene has been implicated as a major risk factor in this process. The aim of this FDG-PET study was to assess the ApoE e4 dose related effect on regional cerebral glucose metabolism (METglc) in clinical AD patients, with statistical voxel based methods. METHODS: Eighty six consecutive mild to moderate AD patients included in the Network for Efficiency and Standardisation of Dementia Diagnosis database underwent FDG-PET scans at rest. PCR was used to determine the ApoE genotype. Patients were grouped as e4 non-carriers (n = 46), e3/e4 (n = 27) and e4/e4 (n = 13) carriers. A voxel-based mapping program was used to compare each AD subgroup with a database of 35 sex and age matched controls (p<0.001, corrected for cluster extent) and also to compare between the subgroups (p<0.001, uncorrected). RESULTS: No difference was found as to age at examination, age at onset, sex, disease duration, educational level, or severity of dementia between AD subgroups. Compared with controls, all AD subgroups had equivalent METglc reductions in the precuneus, posterior cingulate, parietotemporal, and frontal regions. Direct comparisons between AD subgroups indicated that patients with at least one e4 allele had METglc reductions within additional associative and limbic areas compared with e4 non-carriers. CONCLUSIONS: The present FDG-PET study showed different metabolic phenotypes related to the ApoE genotype in clinical AD patients, as revealed with voxel based statistical methods. The results suggest a generalised disorder in e4 carriers impairing metabolism globally, in addition to the more localised changes typical of AD patients.
AIM: In patients with ischemic cardiomyopathy, the differentiation of dysfunctional myocardium in scarred versus hibernating is oversimplified. We evaluated a more complex classification using an imaging technique currently employed for viability detection, having as reference the postrevascularization outcome of dysfunctional segments. METHODS: In 35 patients, we performed gated single-photon emission computed tomography (SPECT) (resting and nitrate-enhanced study, the latter with baseline and dobutamine acquisition) before revascularization. The outcome after revascularization was assessed by repeating resting gated SPECT. Dysfunctional segments without functional recovery in postrevascularization gated SPECT were defined scar (either nontransmural or transmural according to tracer activity); those with recovery were divided in stunned (unchanged uptake) or hibernating (improved postrevascularization activity). This reference classification was compared with the categorization based on prerevascularization gated SPECT. RESULTS: Contractile reserve in dobutamine gated SPECT differentiated scarred from viable segments with 78% accuracy. Tracer activity in nitrate imaging distinguished the degree of transmurality. Nitrate-induced activity increase was significantly higher (p<0.0001) in the hibernating segments (14.9+/-20.4%) than in transmural (4.8+/-13.4%) nontransmural scars (3.3+/-13%), or stunned segments (2.2+/-8%). The presence or absence of nitrate-induced activity increase predicted the postrevascularization perfusion changes in viable myocardium and differentiated hibernating from stunned segments. The prerevascularization classification showed a good agreement with the reference categorization (kappa=0.50). Conclusion. Combining contractile reserve evaluation and perfusion quantification within a single study with baseline-nitrate gated SPECT and dobutamine test it is possible to achieve a comprehensive classification of dysfunctional segments.
This FDG-PET study with SPM99 compared 46 patients with sporadic Alzheimer disease (SAD) to 40 patients with familial AD (FAD) and to 35 matched controls. AD groups had equivalent metabolic (METglu) reductions in several cortical and limbic areas with respect to the controls. Patients with FAD showed decreased METglu in the posterior cingulate, parahippocampal, and occipital cortex as compared to the patients with SAD (p < 0.001). Genetic factors lead to phenotypic differences in AD.
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Acceptance of technetium-99m sestamibi as a tracer of myocardial viability is growing, particularly when nitrate-enhanced imaging is used. However, few data are available on the ability of 99mTc-sestamibi to predict the evolution of global left ventricular ejection fraction (EF). The aim of this study was to examine the ability of resting and nitrate 99mTc-sestamibi single-photon emission tomography (SPET) to predict EF changes after revascularisation in patients who have chronic coronary artery disease with left ventricular dysfunction. Using baseline resting and nitrate 99mTc-sestamibi SPET, we studied 61 patients scheduled for revascularisation because of left ventricular dysfunction. EF was estimated using two-dimensional echocardiography before and after the intervention. A post-revascularisation improvement of > or =5 EF units was defined as significant. Using a 13-segment model, 99mTc-sestamibi activity was quantified and the nitrate-induced activity changes calculated. Three different criteria for detecting viability (defined as post-revascularisation reversible dysfunction) in asynergic segments were compared: (1) resting 99mTc-sestamibi activity > or =60%; (2) nitrate 99mTc-sestamibi activity > or =65%; and (3) nitrate-induced increase >+10% or nitrate-induced increase < or =+10% and nitrate activity > or =65%. EF increased significantly in 32 patients. The number of viable asynergic segments was significantly higher in these patients than in the remaining 29 subjects, and the difference was greater (P<0.0002) using definition (3) than using either baseline (P<0.002) or nitrate activity (P<0.0005). There was a significant relationship between EF changes and number of viable asynergic segments: Spearman R=0.38, P<0.005 using baseline; Spearman R=0.39, P<0.002 using nitrate activity; and Spearman R=0.55, P<0.000005 using definition (3). According to receiver operating characteristic (ROC) curve analysis, this last criterion achieved the best results (81% sensitivity, 69% specificity and 75% accuracy), with an area under the ROC curve of 0.838; this area was significantly larger than when using either baseline (0.744, P<0.02) or nitrate activity (0.747, P<0.005). 99mTc-sestamibi SPET appears able to predict the evolution of global left ventricular EF after revascularisation, thereby confirming the value of 99mTc-sestamibi as a tracer of myocardial viability. The combination of baseline resting and nitrate imaging seems to significantly improve the diagnostic accuracy of 99mTc-sestamibi SPET for this particular purpose.
The synthesis and a preliminary biological characterization of a new class of N-benzyl-aminoalcohols which have serotonin (5-HT(2)) and dopamine (D(2)) receptor affinity is described. In vitro competition binding studies were conducted with the new molecules and (3)H-spiperone on crude membrane preparation from rat striatum and frontal cortex. One of these compounds, 3-benzylamino-1-(4-fluoro-2-iodophenyl)-propan-1-ol (6f), whose IC(50) values are in the micromolar range for both the D(2) and 5-HT(2) receptors, was prepared in iodine-125 labelled form (6i) by nucleophilic substitution of the bromine atom of 3-benzylamino-1-(2-bromo-4-fluorophenyl)-propan-1-ol (6d). In the in vivo studies, conducted on rats, the radiolabelled molecule 6i shows a good capacity to cross the blood-brain barrier (BBB) with a mean value of first pass cerebral extraction (E) of ca. 50% when the regional cerebral blood flow, measured with microsphere technique, is in the experimental animal's physiologic range (0.8-1 mL/min/g). A preliminary in vitro autoradiographic distribution on coronal rat brain slices of the radioiodinated molecule showed that it was preferentially localized in the striatum and in the cerebral regions rich in dopamine- and serotonin receptors, even if a high non-specific binding was observed.
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The purpose of this study was to characterise the nature of the baseline perfusion defects found in patients with Behçet's disease using hexamethylpropylene amine oxime single-photon emission tomography in conjunction with acetazolamide test (Acz SPET). Eleven patients underwent both baseline and Acz SPET. Regions of interest (ROIs) were drawn on the areas with decreased perfusion (D-ROI) and, in the same section, on areas with normal perfusion (N-ROI). The ROIs were then repositioned on the corresponding section on Acz SPET. The mean ROI counts were then transformed into a perfusion index value (PIV) with reference to the global brain counts. In total we found 24 D-ROIs (17 in the cortical and 7 in subcortical grey matter). The influence of Acz infusion was selectively registered in the D-ROIs, where PIVs changed from 1.23+/-0.17 (baseline SPET) to 1.63+/-0.23 (Acz SPET) (P<0.001). No significant difference was seen in the N-ROIs (1.46+/-0.21 and 1.40+/-0.17, respectively, on baseline SPET and Acz SPET). Our results demonstrate that Acz infusion increases the regional cerebral blood flow within baseline grey matter perfusion defects. This finding suggests that baseline perfusion abnormalities could reflect a disconnection rather than local vasculitic involvement.
OBJECTIVES: The aim of the study was to verify the prognostic implications of viability detection using baseline-nitrate sestamibi imaging in patients with left ventricular (LV) dysfunction due to chronic coronary artery disease (CAD) submitted to different therapeutic strategies. BACKGROUND: The prognostic meaning of preserved viability in these patients is still debated. Sestamibi is increasingly used for myocardial perfusion scintigraphy and is being accepted also as viability tracer, but no data are available about the relationship between viability in sestamibi imaging, subsequent treatment, and patient's outcome. METHODS: Follow-up data were collected in 105 CAD patients with LV dysfunction who had undergone baseline-nitrate sestamibi perfusion imaging for viability assessment and had been later treated medically (group 1), or submitted to revascularization, which was either complete (group 2A) or incomplete (group 2B). RESULTS: Eighteen hard events (cardiac death or nonfatal myocardial infarction) were registered during the follow-up. A significantly worse event-free survival curve was observed in the patients of group 1 (p < 0.0002) and group 2B (p < 0.03) compared to those of group 2A. Using a Cox proportional hazard model, the most powerful prognostic predictors of events were the number of nonrevascularized asynergic segments with viability in sestamibi imaging (p < 0.003, risk ratio [RR] = 1.4), and the severity of CAD (p < 0.02, RR = 1.28). CONCLUSIONS: Viability detection in sestamibi imaging has important prognostic implications in CAD patients with LV dysfunction. Patients with preserved viability kept on medical therapy or submitted to incomplete revascularization represent high-risk groups.
OBJECTIVE: The concept that gut inflammation is implicated in the pathogenesis of spondyloarthropathies (SpA) has long been considered. Subclinical intestinal inflammation has been reported in adult patients with SpA by histological examination of intestinal biopsies. We assessed the presence of gut inflammation by abdominal 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO) labeled leukocyte scintigraphy in a group of children and adolescents with HLA-B27 positive SpA without gastrointestinal (GI) symptoms, and correlated the scintigraphic results to disease activity. METHODS: Abdominal scintigraphy with 99mTc-HMPAO labeled leukocytes was performed in 27 HLA-B27 positive children and adolescents with SpA without GI symptoms. Patients were divided into 2 groups according to the presence of active or inactive joint disease: Group A, 17 patients with active disease, and Group B, 10 patients with inactive disease. Patients with positive abdominal scintigraphy underwent complete bowel investigation by means of small bowel barium follow-through, abdominal ultrasound scan, and ileocolonoscopy with mucosal biopsies. RESULTS: Thirteen of 27 patients (48%) had scintigraphy indicating the presence of bowel inflammation. All patients with abnormal scan had active joint disease, whereas no patient with inactive disease had a positive intestinal uptake of labeled leukocytes. Bowel investigation revealed the presence of aspecific mucosal inflammatory changes in the majority of patients with positive scintigraphy. CONCLUSION: The presence of intestinal leukocyte uptake only in patients with active joint disease, even if intestinal inflammatory changes were minimal and clinical gut manifestations were absent, supports the role of gut inflammation in the pathogenesis of joint disease in HLA-B27 positive patients with SpA.
The significance of reverse redistribution on rest-redistribution thallium-201 myocardial scintigraphy is unclear. Previous studies suggested that reverse redistribution segments with normal resting activity include viable myocardium, whilst resting defects with further worsening correspond to scar. We evaluated whether reverse redistribution has an independent significance for the prediction of post-revascularization recovery, particularly as compared with the quantification of redistribution activity. We studied 26 coronary artery disease patients with left ventricular dysfunction, who underwent 201Tl rest-redistribution single-photon emission tomography (SPET) and echocardiography before revascularization. Viability was defined by the detection of wall motion improvement on follow-up echocardiography. 201Tl activity was considered normal if >/=80%, moderately reduced if <80% but >/=50%, and severely decreased if <50%. Reverse redistribution was defined as a defect in redistribution images with >/=10% decrease in relative 201Tl activity compared with the resting value. Reverse redistribution was detected in 33 segments (10%). Baseline dysfunction was equally observed in the reverse redistribution and in the non-reverse redistribution segments (64% vs 56%, P=0.40) and the rate of asynergic segments with post-revascularization recovery was not different between the two groups (33% vs 54%, P=0.11). The rate of functional recovery in redistribution defects without reverse redistribution was 53% in moderate and 30% in severe defects; the corresponding values for the reverse redistribution segments were 50% and 27% (all non-significant versus non-reverse redistribution segments). For the prediction of post-revascularization recovery in asynergic segments, the detection of reverse redistribution on rest-redistribution 201Tl SPET does not add any information to the quantitative analysis of redistribution activity.