Cognitive reserve maps the core loci of neurodegeneration in corticobasal degeneration.

BACKGROUND AND PURPOSE: Cognitively stimulating life experiences and activities are deemed to moderate the clinical impact of brain damage progressively building a neural and cognitive reserve (CR). CR has been studied extensively in various neurodegenerative disorders, but not in corticobasal degeneration (CBD). METHODS: Using Statistical Parametric Mapping 8, years of education, as a determinant of CR, was correlated with tracer uptake on positron emission tomography with 18 F-fluorodeoxyglucose, as a marker of neurodegeneration, in 35 patients with various phenotypes of CBD, including a cognitive-motor composite score or symptoms duration as covariates for controlling disease stage. RESULTS: A cluster of relative hypometabolism was found associated with higher education in the left inferior regions of pre- and post-rolandic gyri and insula, which represent typical loci of neurodegeneration in CBD regardless of clinical presentation. CONCLUSIONS: The present findings extend to CBD the evidence gathered in other neurodegenerative disorders that a higher CR has a protective effect against the clinical manifestations of brain degeneration.

(11)C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients.

PURPOSE: To evaluate, in prostate cancer (PCa) patients the potential of (11)C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. METHODS: We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on (11)C-choline PET/CT only at the LN site. (11)C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. RESULTS: PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. CONCLUSION: (11)C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated (11)C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate.

Spontaneous regression of hepatitis B virus-associated cirrhosis developed in childhood.

We reported two cases of hepatitis B virus infection-related cirrhosis developed during childhood and followed up for more than 20 years. Both the subjects remained untreated, and ultimately regression of cirrhosis was documented by clinical (including ultrasound) and histological examination. Recent studies have already suggested that hepatitis B virus-related cirrhosis may regress after treatment, but this is the first demonstration that hepatitis B virus-associated cirrhosis developed in childhood may be a spontaneously reversible process. Subsidence of virus replication and of necro-inflammatory process and the efficiency of liver regeneration and repair might contribute to this favourable outcome.

Skewing of the T-cell receptor repertoire in the lung of patients with HIV-1 infection.

OBJECTIVES: A bias of the use of T-cell receptor (TCR) V beta regions has been reported both in peripheral blood and in several tissues in patients with AIDS, including lymph nodes, spleen and salivary glands. Although the disease is frequently characterized by an infiltration of T cells in the lung interstitium, no information is presently available on the configuration of the TCR repertoire in this microenvironment. This study was performed to address the question of whether a bias in T-cell selection occurs in the lung of patients with AIDS. METHODS: TCR beta-chain variable region (TCR-V beta) repertoire was analysed by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 13 patients with HIV-1 infection at different stages of the disease. Blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins (SEA, SEB, SEC1, SEC2, SED and SEE). RESULTS: Flow cytometry analysis in AIDS patients demonstrated an overexpression of cells bearing V beta 2 and V beta 3 gene segments in the lung compared with peripheral blood of the same subjects, as well as to lung and blood lymphocytes of normal controls. PCR analysis performed in AIDS patients extended these observations and demonstrated a significant bias also in the use of T cells bearing V beta 7 and V beta 9 gene regions in the lung compartment with respect to the blood. Virtually all T cells bearing the overrepresented V beta segment belong to the CD8 subset. Interestingly, T-lymphocyte response to different superantigens demonstrated a low proliferative rate in the lung with respect to the blood in HIV-1-infected patients. CONCLUSIONS: These findings indicate a compartmentalization of cells bearing discrete V beta gene products in the pulmonary microenvironment of patients with AIDS and suggest that the expansion of specific-V beta region subsets occurring in the lung might result from triggering by a superantigen.

HIV-1 infection of the thymus: evidence for a cytopathic and thymotropic viral variant in vivo.

As thymocyte infection may represent one of the mechanisms responsible for CD4+ T lymphocyte depletion in HIV-1-infected individuals, we studied the occurrence of HIV-1 infection in the thymus in vivo. Thymus (THYPD) and peripheral blood (PBLPD) primary viral isolates were obtained from an HIV-1-infected patient; restriction pattern analysis revealed the presence of a viral variant (THY) in the thymus isolate, from which biological viral clones containing this variant were obtained by limiting dilution infection of Molt-3 cells. The biological phenotype of the viral isolates and THY clones was studied in different cell lines and primary cultures. PBLPD, THYPD, and THY clones could efficiently infect T cell lines; the thymic variant showed a higher cytopathic activity in T cell lines, and a higher replication capacity in both unfractionated and CD4+CD8(+)-enriched primary thymocytes. Sequence analysis of the viral population patterns in vivo confirmed the presence of the THY variant in the thymic compartment, and revealed that the degree of V3 loop heterogeneity was higher in the thymocytes of the patient than in the peripheral blood lymphocytes. In addition to confirming thymocyte infection in vivo, our data also indicate that a differential distribution of viral variants may occur among different body compartments in a single individual; the emergence of cytopathic and tissue-specific variants in the thymus may play a relevant role in the pathogenesis of HIV-1 disease.

Hepatitis C in childhood: epidemiological and clinical aspects.

Hepatitis C virus (HCV) is responsible for most cases of chronic non-A, non-B hepatitis in multi-transfused children, but has been also implicated in at least one third of cases without history of parenteral exposure. We have recently evaluated the natural history of chronic hepatitis C in 37 children without underlying systemic diseases. None of the patients had a history of acute hepatitis and only 22 were symptomatic at presentation. Liver histology was consistent with active liver disease of mild to moderate activity in 42% of cases (one child had cirrhosis) and with persistent or lobular hepatitis in the remaining cases. During a mean follow-up period of 3.4 +/- 3.2 years symptoms were rarely observed and none of the patients developed liver failure, but 97% maintained abnormal alanine-aminotransferase levels. These results suggest that chronic hepatitis C in children, at least in its early stage, is a mild disease infrequently associated with severe liver lesions; however the persistence of liver damage over the years raises questions about the long-term outcome of the illness and about the rationale of antiviral therapy.

Pituitary macroadenoma and Cushing's disease in pediatric patients: patient report and review of the literature.

Cushing's syndrome in pediatric patients has been rarely reported and most of the cases are due to adrenal tumors. When the etiology is an ACTH-secreting pituitary adenoma, most often it is a microadenoma. We report on a 9 year-old girl with an ACTH-secreting macroadenoma, whose surgical removal through transsphenoidal approach was extremely difficult due to invasion of the cavernous sinus as well as adjacent structures. After two surgical approaches and stereotactic radiotherapy, she still suffers from the deleterious effects of hypercortisolism, especially marked osteoporosis with vertebral collapse, which interferes with her walking and causes excruciating pain. Two months after the radiotherapy, we still had doubts about the prognosis regarding the persistence of the hypercortisolism. From six months on, her general health started improving, she lost weight, the backache disappeared and her cortisol level returned to normal.

Unusual presentation of sarcoid-like reaction on bone marrow level associated with mediastinal lymphadenopathy on (18)F-FDG-PET/CT resembling an early recurrence of Hodgkin's Lymphoma.

(18)F-FDG-PET/CT is widely employed to evaluate lymphoma patients. False positive results are quite frequent, generally due to active phase of inflammation. We describe an unusual PET/CT presentation of a sarcoid-like reaction (SLR) in a patient monitored for Hodgkin Lymphoma characterized by an intense uptake in lymph nodes and multiple bone foci in a PET/CT study. The final diagnosis was obtained by biopsy. This study draws attention to the fact that multifocal bone marrow uptakes due to a sarcoideal reaction may be a possible cause of false positive results in (18)F-FDG-PET/CT studies in oncology patients.

PET/CT and contrast enhanced CT in single vs. two separate sessions: a cost analysis study.

AIM: Aim of the study was to quantify the economic impact of PET/CT and contrast enhanced (c.e.) CT performed in a single session examination vs. stand-alone modalities in oncological patients. METHODS: One-hundred-forty-five cancer patients referred to both PET/CT and c.e. CT, to either stage (N.=46) or re-stage (N.=99) the disease, were included. Seventy-two/145 performed both studies in a single session (innovative method) and 73/145 in two different sessions (traditional method). The cost-minimization analysis was performed by evaluating: 1) institutional costs, data obtained by hospital accountability (staff, medical materials, equipment maintenance and depreciation, departments utilities); 2) patients costs, data obtained by a specific survey provided to patients (travel, food, accommodation costs, productivity loss). RESULTS: Economic data analysis showed that the costs for innovative method was lower than those of traditional method, both for Institution (106 € less per test) and for patient (21 € less per patient). The loss of productivity for patient and caregivers resulted lower for the innovative method than the traditional method (3 work-hour less per person). CONCLUSION: PET/CT and c.e. CT performed in a single session is more cost-effective than stand-alone modalities, by reducing both Institutional and patients costs. These advantages are mainly due to lower Institutional cost (single procedure) and to lower cost related to travel and housing.

Performance of a SPECT collimator-detector response reconstruction algorithm: phantom studies and validation in inflammation clinical studies.

AIM: To evaluate evolution for bone (EfB), one of the recent corrective collimator detector response (CDR) image reconstruction packages, resolution recovery and iterative reconstruction protocols were compared to the standard Filtered Back Projection (FBP) protocol and the possibility of time reduced acquisition (15 instead of 30 seconds/projection) was evaluated. METHODS: Tomographic spatial resolution, contrast, noise and signal-to-noise ratio (SNR) were analyzed in phantom studies. Patient studies were conducted on sixteen [99mTc]HMPAO labeled leukocyte patients with suspected local inflammation, submitted to SPECT/CT and conventional leukocyte scintigraphy. Target background ratio (TBR) and boundary of each lesion were calculated. Images were also analyzed by visual inspection by two blinded expert physicians. RESULTS: a) Phantom: resolution in phantom improves with the use of EfB mainly due to iterative reconstruction methods vs FBP. EfB shows a reduction in noise. No differences were found in contrast data, while SNR changes were mainly due to changes in noise. Time reduction, while increasing image noise, does not modify resolution; nevertheless, half-time EfB noise is the same as full-time FBP noise. b) PATIENTS: lesion boundary is better defined in patient studies using iterative reconstruction vs FBP; no changes were observed for CDR vs iterative OSEM, or for full-time vs half-time acquisition. TBR is comparable in iterative and FBP protocols, while it is improved by EfB. At visual inspection, a higher score is always associated with EfB. CONCLUSION: Resolution, noise, SNR and TBR improve when applying the resolution recovery. EfB permits reduction of acquisition time without compromising image quality.

PET-CT for treatment planning in prostate cancer.

UNLABELLED: Molecular imaging techniques, such as positron emission tomography (PET), may be of help in management treatment planning. In particular, in prostate cancer patients, PET and PET-computed tomography (PET-CT) can be successfully used in treatment planning at different steps, including: 1) tumor characterization and staging, to define the most appropriate primary treatment; 2) re-staging, to define a second line therapy on the site of possible recurrences; and 3) monitoring the disease and the efficacy of treatment. Although the most commonly used PET tracer, [(18)F]Fluorodeoxyglucose ([(18)F]FDG), presents limitations in imaging prostate cancer patients, several alternative PET tracers have been proposed to evaluate by PET these patients, with promising RESULTS: Optimal treatment for prostate cancer depends on the accuracy in tumor characterization and staging. In fact, localized primary tumor can be treated with radical prostatectomy, while metastatic tumor is usually treated with systemic therapeutic regimen. Different PET tracers, including [(11)C]Choline, [(18)F]Choline and [(11)C]Acetate, have been successfully reported. Howe-ver, further studies in large population of patients are still necessary to establish their final clinical role in the primary detection and staging of prostate cancer. The information on the site of possible recurrences is also important for therapeutic strategies. Several PET tracers have been proposed to re-stage prostate cancer patients. In particular, [11C]Choline PET has now been established as a clinical procedure to non-invasively re-stage, in a single session, prostate cancer patients presenting an increase of prostate specific antigen (PSA) after radical treatment. The role of PET and PET-CT in monitoring the disease and the effects of treatment are under investigation and still to be defined. In the present review, we focused on the use of several PET tracers in different clinical indications aimed at the treatment planning of prostate cancer patients.

18F-FDG-PET/CT guiding to diagnosis of neurosarcoidosis / 18F-FDG-PET/TC para guiar el diagnóstico de neurosarcoidosis

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Integrated PET/CT as a first-line re-staging modality in patients with suspected recurrence of ovarian cancer.

PURPOSE: The aims of this study were to compare CT with PET/CT results in patients with suspected ovarian cancer recurrence and to assess the impact of the PET/CT findings on their clinical management. METHODS: Thirty-two consecutive patients with suspected ovarian cancer recurrence were retrospectively included in the study. Abdominal contrast-enhanced CT and PET/CT with [(18)F]FDG, in addition to conventional follow-up, were performed in all 32 patients. After the comparison between CT and PET/CT results, based on clinical reports, changes in the clinical management of patients (intermodality changes) due to PET/CT information were analysed. RESULTS: Twenty of the 32 patients were positive at CT (62.5%) versus 29 (90.6%) at PET/CT. Intermodality changes in management, i.e. use of a different treatment modality, after PET/CT examination were indicated in 14/32 (44%) patients. In particular, before PET/CT study, the planned management was as follows: wait-and-see in 7/32 (22%), further instrumental examinations in 4/32 (12%), chemotherapy in 10/32 (31%), diagnostic surgical treatment in 6/32 (19%) and surgical treatment in the remaining 5/32 (16%). After PET/CT study, wait-and-see was indicated in 1/32 (3%), further instrumental examinations in 7/32 (22%), chemotherapy in 16/32 (50%), diagnostic surgical treatment in 2/32 (6%) and surgical treatment in the remaining 6/32 (19%). CONCLUSION: Integrated PET/CT could detect tumour relapse in a higher percentage of patients than could CT. A change in the clinical management was observed in 44% of cases when PET/CT information was added to conventional follow-up findings.

Contained rupture of common iliac artery aneurysm in a contrast-enhanced PET/CT study / Rotura contenida de un aneurisma de la arteria iliaca común en estudio PET/TAC con medio de contraste

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[Graves' disease. Clinical features and treatment results]. / Morbus Basedow: Klinik und Behandlungsergebnisse.

In the last years the diagnosis of Grave's disease has become easier and accelerated due to new laboratory and instrumental tests. The therapeutic possibilities improved also by using antithyroidal drugs, surgery and radioiodine application subsequently. In a retrospective study 278 outpatients with Graves disease, treated and controlled by our centre for thyroid diseases in 1992-1999, were investigated to evaluate the initial and leading subjective symptoms which led the patients to seek medical help ("guide symptoms"). These obtained guide symptoms were compared with the objective "clinical signs" observed at the beginning of the disease. Weight loss turned out to be the most frequent (26%) guide symptom, whereas tachycardia (> 90 beats/min) and moist skin were the most frequently observed clinical signs (71 and 61% respectively). The beginning of therapy, dosage of drugs, length of application and results of treatment are critically evaluated, with special emphasis on the rate and time of remission, on the frequency of recurrences and on the success of additional treatments such as surgery and/or radioiodine application. Pharmacological treatment alone induced a persistent remission (at least 6 months of euthyroidism) in 156 patients (in 113 after the first and in 43 after the 2nd drug trial). Surgery was successful in 46, radioiodine application in 40 patients. The sequential use of drug therapy, surgery and radioiodine as it is performed in our institution leads to a permanent remission in 242 of 278 (= 87%) patients.