RESUMO
Interventional Radiology (IR) deals with the diagnosis and treatment of various diseases through medically guided imaging. It provides unquestionable benefits to patients, but requires, in many cases, the use of high doses of ionizing radiation with a high impact on radiation risks to patients and to overall dose to the population. The International Commission on Radiological Protection introduced Diagnostic reference levels (DRLs) as an effective tool to facilitate dose verification and optimize protection for patients undergoing radiological procedures. In addition, EURATOM Council Directive 2013/59 and its Italian transposition (Legislative Decree 101/2020) have reiterated that DRLs must be established for many common radiological diagnostic procedures to compare the radiation dose delivered for the same diagnostic examination. Within this framework, Istituto Superiore di Sanità-Italian National Institute of Health (ISS)-, in collaboration with relevant Italian Scientific Societies, has provided documents on DRLs in radiological practices such as diagnostic and IR and diagnostic nuclear medicine. These reference documents enable National Hospitals to comply national regulation. The implementation of DRLs in IR is a difficult task because of the wide distribution of doses to patients even within the same procedure. Some studies have revealed that the amount of radiation in IR procedures is influenced more by the complexity of the procedure than by the weight of the patient, so complexity should be included in the definition of DRLs. For this reason, ISS promoted a survey among a sample of Italian Centers update national DRL in IR procedures with related complexity factors than can be useful for other radiological centers and to standardize the DRLs values. In the present paper the procedural methodology developed by ISS and used for the survey will be illustrated.
Assuntos
Níveis de Referência de Diagnóstico , Radiologia Intervencionista , Humanos , Doses de Radiação , Radiografia , Itália , Valores de ReferênciaRESUMO
BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular cancer (HCC) on the waiting list for liver transplantation may be associated with an increased risk for hepatic artery complications. The present study aims to assess the risk for, primarily, intraoperative technical hepatic artery problems and, secondarily, postoperative hepatic artery complications encountered in patients who received TACE before liver transplantation. METHODS: Available data from HCC liver transplantation recipients across six European centres from January 2007 to December 2018 were analysed in a 1 : 1 propensity score-matched cohort (TACE versus no TACE). Incidences of intraoperative hepatic artery interventions and postoperative hepatic artery complications were compared. RESULTS: Data on postoperative hepatic artery complications were available in all 876 patients (425 patients with TACE and 451 patients without TACE). Fifty-eight (6.6 per cent) patients experienced postoperative hepatic artery complications. In total 253 patients who had undergone TACE could be matched to controls. In the matched cohort TACE was not associated with a composite of hepatic artery complications (OR 1.73, 95 per cent c.i. 0.82 to 3.63, P = 0.149). Data on intraoperative hepatic artery interventions were available in 825 patients (422 patients with TACE and 403 without TACE). Intraoperative hepatic artery interventions were necessary in 69 (8.4 per cent) patients. In the matched cohort TACE was not associated with an increased incidence of intraoperative hepatic artery interventions (OR 0.94, 95 per cent c.i. 0.49 to 1.83, P = 0.870). CONCLUSION: In otherwise matched patients with HCC intended for liver transplantation, TACE treatment before transplantation was not associated with higher risk of technical vascular issues or hepatic artery complications.
Lay Summary Patients with liver cancer may be treated with transarterial chemoembolization (TACE) during the period on the transplant waiting list. With TACE, chemotherapeutic coils are injected directly into the small arteries supplying the tumour, after which these vessels are closed. The aim of this therapy is to decrease the tumour size and slow down tumour growth. However, concerns are raised that manipulation of the main hepatic artery by TACE may cause damage to the artery itself. If this would result in problems during or after liver transplantation when the artery is connected to the artery supplying the donor liver, this may endanger the donor liver graft survival. The present study shows no increased risk in problems to connect the artery during liver transplantation after TACE treatment. Also, arterial complications after liver transplantation did not occur more frequently if patients had received TACE treatment. The authors therefore conclude that TACE treatment before liver transplantation could be considered a safe approach.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/métodos , Doenças Vasculares/etiologia , Europa (Continente)/epidemiologia , Feminino , Artéria Hepática , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Fatores de Risco , Taxa de Sobrevida/tendências , Doenças Vasculares/epidemiologia , Listas de EsperaRESUMO
The hereditary spastic paraplegias (HSP) are characterized by spastic gait with weakness in the legs and additional neurological or extra-neurological signs in "complicated" forms. The past two decades have witnessed major advances in our understanding of their molecular bases with the identification of a plethora of loci and the cloning of several SPG genes. Combined genetic and clinical information has permitted a modern, molecularly-driven classification and an improved diagnosis, with several new data on the possible disease mechanisms. Further heterogeneity will rapidly emerge with the diffusion of next-generation sequencing platforms and, under the shadow of common themes in the pathogenesis, new therapeutic options will likely emerge for a great number of patients.
RESUMO
Scleroderma is a group of rare chronic connective tissue disorders characterized by collagen accumulation that causes tissue hardening with consequent fibrosis. Skin involvement is mostly frequent, although several internal organs can be impaired (heart, lungs, liver, etc.). In childhood, juvenile localized scleroderma (JLS) is more frequently observed; in this subtype cutaneous lesions predominate frequently on the limbs but also on the face and scalp; in this case, it is referred to as scleroderma "en coup de sabre" (ECDS). Neurological abnormalities have been described in association with ECDS as an effect of progressive scalp and underlying tissues involvement. Up to now, no validated biomarkers exist to evaluate disease evolution and, in this way, frequently diagnosis of central nervous system (CNS) involvement occurs when patients are already symptomatic. We describe the case of a 5-year old girl, with a diagnosis of ECDS characterized by the typical scalp lesion, with slight subsidence of the underlying diploe. In this case, radiological examination has been essential to evaluate the degree of progression of skin and soft tissues lesions and to clarify the right therapeutic approach. In selected JLS children, both MRI and CT with 3D reconstruction images provide a useful tool to monitor disease evolution and to address therapeutic choices.
Assuntos
Neuroimagem , Esclerodermia Localizada/diagnóstico , Pré-Escolar , Feminino , Humanos , Couro CabeludoRESUMO
Several epidemiological studies showed that gestational diabetes mellitus is the most frequent metabolic disorder of pregnancy, the pathogenesis of which has yet to be completely clarified. The aim of this study was to investigate the presence and processing of caspase 3 (Casp3) and poly(ADP-ribose) polymerase 1 (PARP1) in cord blood lymphocytes as markers of apoptosis in relation to glycaemic control during intrauterine life. Our results showed a specific positive correlation between the levels of active Casp3 (17-19 kDa) and the inactive form of PARP1 (89 kDa) in lymphocytes isolated from newborn babies of diabetic women with unbalanced glycaemic control, with a direct correlation between the activation of casp3 and the inactivation of PARP1, that makes lymphocytes unresponsive towards lipopolysaccharide stimulation, highlighting an altered functional response. Besides more studies are required to fully correlate the activation of the apoptotic process during the intrauterine life with the foetal health later in life, our study indicates that a cord blood lymphocyte, an easily accessible source, is informative about the activation of apoptotic stimuli in circulating cells of newborn babies in relation to the glycaemic control reached by the mother during pregnancy.
Assuntos
Caspase 3/sangue , Diabetes Gestacional/sangue , Linfócitos/metabolismo , Poli(ADP-Ribose) Polimerases/sangue , Adulto , Glicemia/metabolismo , Caspase 3/genética , Proliferação de Células , Ativação Enzimática , Feminino , Sangue Fetal/enzimologia , Humanos , Recém-Nascido , Linfócitos/citologia , Poli(ADP-Ribose) Polimerase-1 , GravidezRESUMO
Since levodopa-induced peak dyskinesias (LIDs) may reflect, in part, a disproportionate phasic release of dopamine from synaptic vesicles, we examined the ability of the vesicular depletor tetrabenazine (TBZ) to reduce LIDs in 10 dyskinetic advanced Parkinson's disease (PD) patients. After basal evaluation, the patients received, through a slow titration, oral TBZ twice a day for six weeks (up to 50 mg daily) before being re-assessed after a challenge with levodopa. The primary outcome measure was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) dyskinesia score (items 32 to 34). TBZ was well tolerated. A clear treatment effect on LIDs emerged (up to 45%, p<0.05). In two patients a little worsening of motor performance necessitated an increase of the antiparkinsonian therapy, which did not worsen peak-dose LIDs. The patients experienced a clear benefit in terms of their quality of life. In this open-label pilot study, orally administered TBZ resulted in objective and subjective improvements in LIDs. Larger pharmacological studies are in progress.
Assuntos
Antiparkinsonianos/efeitos adversos , Dopaminérgicos/efeitos adversos , Discinesias/tratamento farmacológico , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Tetrabenazina/uso terapêutico , Idoso , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/uso terapêutico , Dopamina/metabolismo , Dopaminérgicos/administração & dosagem , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Levodopa/administração & dosagem , Levodopa/uso terapêutico , MasculinoRESUMO
PURPOSE: The authors evaluated the prognostic role of 18-fluoro-fluorodeoxyglucose positron emission tomography/multidetector computed tomography ([(18)F]-FDG PET/MDCT) in treating patients with Hodgkin's lymphoma (HL). MATERIALS AND METHODS: We retrospectively evaluated 132 patients with HL studied with PET/MDCT before the start of chemotherapy (CTX) for staging purposes and again after two CTX cycles with [doxorubicin (Adriblastin), bleomycin, vinblastine, dacarbazine (ABVD_] (interim PET/MDCT), at least 30 days after the end of the last CTX cycle and/or 3 months after the end of radiotherapy, if delivered (final PET-MDCT). RESULTS: Interim PET-MDCT was negative in 104/132 patients (79%), and their final PET-MDCT showed complete remission in 102/104 (98%) of cases, with disease recurrence/persistence in two (2%). In the remaining 28 (21%) patients, interim PET-MDCT revealed an early response in 68% of cases and chemoresistance with disease progression in 32% of cases; in these 28 patients, final PET-MDCT showed a lack of response to treatment in 43% of cases (43%) and complete remission in 57% of cases. Statistical analysis of these data showed that interim PET-MDCT had a negative predictive value of 98% and a positive predictive value of 42%, with values of sensitivity, specificity and diagnostic accuracy of 85.7%, 86.4% and 86.4%, respectively. CONCLUSIONS: Interim PET-MDCT has a reliable prognostic role in diagnosis and treatment of patients with HL, as it helps predict which patients are more likely to achieve a complete response at the end of treatment. PET/MDCT may also lead to a change in treatment, with reduced treatment-related toxic effects and significantly reduced total costs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Doença de Hodgkin/patologia , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Vimblastina/uso terapêuticoRESUMO
This study investigated how the design of surface topography may stimulate stem cell differentiation towards a neural lineage. To this end, hydrogenated amorphous carbon (a-C:H) groove topographies with width/spacing ridges ranging from 80/40µm, 40/30µm and 30/20µm and depth of 24 nm were used as a single mechanotransducer stimulus to generate neural cells from human bone marrow mesenchymal stem cells (hBM-MSCs) in vitro. As comparative experiments, soluble brain-derived neurotrophic factor (BDNF) was used as additional biochemical inducer agent. Despite simultaneous presence of a-C:H micropatterned nanoridges and soluble BDNF resulted in the highest percentage of neuronal-like differentiated cells our findings demonstrate that the surface topography with micropatterned nanoridge width/spacing of 40/30µm (single stimulus) induced hBM-MSCs to acquire neuronal characteristics in the absence of differentiating agents. On the other hand, the alternative a-C:H ridge dimensions tested failed to induce stem cell differentiation towards neuronal properties, thereby suggesting the occurrence of a mechanotransducer effect exerted by optimal nano/microstructure dimensions on the hBM-MSCs responses.
Assuntos
Células-Tronco Mesenquimais/citologia , Nanotubos de Carbono/química , Neurônios/citologia , Astrócitos/citologia , Astrócitos/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais/metabolismo , Neurônios/metabolismoRESUMO
The authors describe an unusual complication after radiofrequency ablation of hepatocellular carcinoma (HCC). An 84-year old man, already operated of right hepatectomy for HCC, underwent radiofrequency ablation (RFA) of a new focal hepatic lesion in IV segment, under ultrasound (US) and computed tomography (CT) guidance. The procedure was carried out without any special difficulties or complications. Seven days later, the patient suddenly complained epigastric pain, progressive jaundice and sleepiness and an increase in cholestasis sierological parameters. A CT scan revealed thrombosis of the left side branch of the portal vein, with moderate bile ducts distension. The case described demonstrates how RFA may cause thermally mediated damage of the surrounding structures, due to unpredictable radio-frequency propagation. The interest of this case report is due to the fact that portal vein thrombosis did not occur immediately after the procedure, it happened without direct vessel injury by the needle and involved a vessel greater than 3 mm.
Assuntos
Ablação por Cateter/efeitos adversos , Veia Porta , Trombose/etiologia , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , MasculinoRESUMO
In regenerative medicine, stem cells are currently considered ideal candidates for the treatment of diseases and injuries of the nervous system, for which, at present, there are no effective treatments. Promising results have been shown by clinical trials for neurodegenerative diseases such as Parkinson's diseases, but also for demyelinising disorders and traumatic lesions of the brain and spinal cord. The proof-of-principle is that the replacement of damaged cells and the restoration of function can be accomplished by the transplantation of embryonic or adult stem cells. Advancements in stem cell biology were recently propelled by the ability to generate induced pluripotent stem (iPS) cells from fibroblasts of several neurodegenerative diseases (e.g. Parkinson's and Huntington's diseases, Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy). In this review, we discuss the molecular basis of stem cell therapy and the advancement of research on regenerative medicine for diseases and injuries of the nervous system.
Assuntos
Doenças Neurodegenerativas/terapia , Doenças do Sistema Nervoso Periférico/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco/metabolismoRESUMO
PURPOSE: The aim of our prospective study was to compare the diagnostic accuracy of early, delayed and dual-time-point positron emission tomography (PET) acquisition with contrast enhanced computed tomography (CT) within a PET-CT examination in the evaluation of pulmonary solitary nodules (SPNs). MATERIALS AND METHODS: Thirty patients were enrolled in the study. All the patients underwent a dual-time-point PET-CT examination. Whole-body PET images were acquired at 50 min after fluorine18-fluorodeoxyglucose ((18)F-FDG) administration (early), followed by a chest acquisition (delayed). Lung nodules with maximum standardised uptake value SUVmax > or =2.5 were considered malignant. SUVmax was calculated on early and delayed images; SUV increasing > or =10% (Delta SUVmax) was considered suggestive of malignancy. Absence of significant lung nodule enhancement (<15 Delta HU) at CT was considered strongly predictive of benignity. For the CT morphological assessment, the irregularity of the shape of each lesion was rated. PET-CT results were related to histological assays and clinical records. Diagnostic accuracy was assessed by area under the receiveroperarting characteristic (ROC) curves analysis. RESULTS: Early and delayed SUVmax of malignant nodules were significantly higher than those of benign disease. Early SUVmax sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 77%, 91%, 79.5% and 66.7%; delayed SUVmax corresponding values were 77%, 66%, 74% and 66%; dual-time-point SUVmax values were 83%, 67%, 75% and 74%; DeltaHU values were 94%, 34%, 67%, 96%; CT morphologic evaluation values were 61%, 46%, 60%, 47%. Area under the curve (AUC) for early SUVmax was 0.79, for delayed SUVmax 0.80, for dual-time-point SUVmax 0.85, for DeltaHU 0.63 and for CT morphologic assessment 0.58. CONCLUSIONS: In our small series of patients, early and delayed SUVmax showed comparable accuracies, whereas morphological and contrast enhanced CT evaluations showed the lowest accuracies. Dual-time-point SUVmax showed the largest AUC. However, dual-time-point SUVmax was most sensitive, whereas single-time-point SUVmax was most specific.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada de Emissão/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Interpretação de Imagem Radiográfica Assistida por Computador , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Imagem Corporal TotalRESUMO
PURPOSE: The aim of this study was to compare the diagnostic accuracy of 2-[fluorine-18] fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) and computed tomography (CT) with PET/CT in the detection of liver metastases during tumour staging in patients suffering from colorectal carcinoma for the purposes of correct surgical planning and follow-up. MATERIALS AND METHODS: A total of 467 patients underwent a PET/CT scan using an iodinated contrast medium. We compared images obtained by the single PET scan, the single CT scan and by the fusion of the two procedures (PET/CT). The final diagnosis was obtained by histological examination and/or by the follow-up of all patients, including those who did not undergo surgery or biopsy. RESULTS: The PET scan had 94.05% sensitivity, 91.60% specificity and 93.36% accuracy; the CT scan had 91.07% sensitivity, 95.42% specificity and 92.29% accuracy. The combined procedures (PET/CT) had the following values: sensitivity 97.92%, specificity 97.71% and accuracy 97.86%. CONCLUSIONS: This study indicates that PET/CT is very useful in staging and restaging patients suffering from colorectal cancer. It was particularly useful when recurrences could not be visualised either clinically or by imaging despite increasing tumour markers, as it guaranteed an earlier diagnosis. PET/CT not only provides high diagnostic performance in terms of sensitivity and specificity, enabling modification of patient treatment, but it is also a unique, high-profile procedure that can produce cost savings.
Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Carcinoma/secundário , Carcinoma/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Feminino , Fluordesoxiglucose F18 , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Autosomal Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum (AR-HSPTCC) is a clinically and genetically heterogeneous complicated form of spastic paraplegia. Two AR-HSPTCC loci have been assigned to chromosome 15q13-15 (SPG11) and chromosome 8p12-p11.21 respectively. Mutations in the SPG11 gene, encoding the spatacsin protein, have been found in the majority of SPG11 families. In this study, involvement of the SPG11 or 8p12-p11.21 loci was investigated in five Italian families, of which four consanguineous. METHODS: Families were tested for linkage to the SPG11 or 8p12-p11.21 loci and the SPG11 gene was screened in all the affected individuals. RESULTS: Linkage was excluded in the four consanguineous families. In the only SPG11-linked family the same homozygous haplotype 4.2 cM across the SPG11 locus was shared by all the three affected siblings. A novel c.2608A>G mutation predicted to affect the splicing was found in exon 14 of the SPG11 gene. DISCUSSION: This collection of families contributes to highlight the intra and inter locus heterogeneity in AR-HSPTCC, already remarked in previous reports. In particular, it confirms heterogeneity amongst Italian families and reports a new mutation predicted to affect splicing in the spatacsin gene.
Assuntos
Agenesia do Corpo Caloso/genética , Predisposição Genética para Doença/genética , Mutação/genética , Malformações do Sistema Nervoso/genética , Proteínas/genética , Paraplegia Espástica Hereditária/genética , Adolescente , Adulto , Agenesia do Corpo Caloso/metabolismo , Agenesia do Corpo Caloso/fisiopatologia , Feminino , Humanos , Masculino , Malformações do Sistema Nervoso/metabolismo , Malformações do Sistema Nervoso/fisiopatologia , Linhagem , Proteínas/metabolismo , Paraplegia Espástica Hereditária/metabolismo , Paraplegia Espástica Hereditária/fisiopatologia , Adulto JovemRESUMO
The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.
Assuntos
Neoplasias da Mama/diagnóstico , Imageamento por Ressonância Magnética , Feminino , HumanosRESUMO
PURPOSE: The objective of this study was to compare conventional breast magnetic resonance imaging (MRI) with breast MRI acquired with the sensitivity-encoding (SENSE) technique on a 1.5-T MRI scanner in the same patient, on the basis of image quality and kinetics analysis. MATERIALS AND METHODS: Thirty-one patients with suspicious mammography and US findings were included in the study. Conventional breast MRI consisted of the following sequences: T1 (matrix, 288 x 512); T2 (matrix 225 x 512); short tau inversion recovery (STIR) (matrix 320 x 224) and dynamic T1 [2D fast-field echo (FFE)] (matrix 256 x 512; temporal resolutionAssuntos
Neoplasias da Mama/diagnóstico
, Aumento da Imagem
, Imageamento por Ressonância Magnética/métodos
, Adulto
, Idoso
, Feminino
, Humanos
, Pessoa de Meia-Idade
, Reprodutibilidade dos Testes
, Sensibilidade e Especificidade
RESUMO
PURPOSE: Histology is the gold standard by which to diagnose and score hepatic fibrosis. Recently, it has been proposed that hepatic magnetic resonance spectroscopy (MRS) could provide an accurate representation of the disease process. The aim of this study was to correlate the in vivo high-field (3-Tesla) (1)H MRS features of noncirrhotic chronic hepatitis C patients stratified according to the histopathological stages of fibrosis. MATERIALS AND METHOD: Six healthy controls and 23 patients with biopsy-proven precirrhotic hepatitic C virus (HCV)-related liver disease were included. The subdivision of patients into the histopathological stages of fibrosis was based on the Ishak fibrosis (F) scoring system: mild hepatitis (0< or =F< or =1), moderate (2< or =F< or =3) and severe hepatitis (4< or =F< or =5). For correlation analysis, the Spearman nonparametric test was used. Differences between groups were calculated with the nonparametric Mann-Whitney U test. A p value <0.05 was considered significant. The particular metabolite content was evaluated in relative units (RU), according to the pattern metabolite/H(2)O=area of the metabolite x1,000/area of nonsuppressed water. RESULT: A significant statistical difference was observed between control vs. mild and moderate vs. severe disease severity in choline-containing compounds (CCC)/H(2)O ratios (p=0.0379 and p=0.0003) and in glutamine/glutamate (Glx)/H(2)O ratios (p=0.004 and p<0.0001), whereas a statistically significant difference in the lipid/H(2)O ratios was achieved only between control vs. moderate and between moderate vs. severe stages of disease (p=0.011 and p=0.0030). CONCLUSION: High-field (1)H MRS successfully differentiates between mild/moderate vs. severe stages of chronic hepatitis and can be considered a complement to most standard imaging protocols in the liver.
Assuntos
Hepatite C Crônica/diagnóstico , Espectroscopia de Ressonância Magnética/métodos , Idoso , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cidade de Roma , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
OBJECTIVE: To perform a clinical and genetic study of two large Italian families (RM-36 and RM-51) showing the cardinal clinical features of Silver syndrome (SS), a rare dominantly inherited form of hereditary spastic paraplegia (HSP) complicated by amyotrophy of the small hand muscles. METHODS: Clinical assessment including neurophysiologic, neuropsychological, and neuroimaging evaluations. Genetic studies included linkage and sequence analyses. RESULTS: Using a genome-wide survey in the RM-36 family, a novel locus (SPG38) has been identified and mapped within the 13.1-cM region on chromosome 4p16-p15 between markers D4S432 and D4S1599. The RM-51 family was linked to the SPG4 locus at 2p21-p24 and sequence analysis of SPG4 showed a novel frameshift mutation p.Asp321GlyfsX6. Clinical examination of the affected members carrying the mutation showed high frequency of additional clinical features including decreased vibration sense, pes cavus, temporal lobe epilepsy, and cognitive impairment. CONCLUSIONS: This study demonstrates evidence of a novel locus SPG38 for Silver syndrome (SS) and suggests that genetic defects in SPG4 might lead to broad clinical features overlapped with those of SS.
Assuntos
Adenosina Trifosfatases/genética , Alelos , Escore Lod , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/patologia , Adolescente , Adulto , Transtornos Cognitivos/genética , Transtornos Cognitivos/patologia , Eletromiografia , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/patologia , Saúde da Família , Feminino , Genes Dominantes , Genômica , Humanos , Imageamento por Ressonância Magnética , Masculino , Condução Nervosa , Linhagem , Fenótipo , Paraplegia Espástica Hereditária/fisiopatologia , EspastinaAssuntos
Adenosina Trifosfatases/genética , Aberrações Cromossômicas , Análise Mutacional de DNA , Genes Dominantes/genética , Genética Populacional , Paraplegia Espástica Hereditária/genética , Adulto , Idade de Início , Idoso , Deleção Cromossômica , Códon sem Sentido/genética , Estudos Transversais , Feminino , Mutação da Fase de Leitura/genética , Triagem de Portadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mutagênese Insercional/genética , Mutação de Sentido Incorreto/genética , Fenótipo , Sítios de Splice de RNA/genética , Paraplegia Espástica Hereditária/epidemiologia , EspastinaRESUMO
It has been shown that lysosomes are involved in B cell apoptosis but lysosomal glycohydrolases have never been investigated during this event. In this study we determined the enzymatic activities of some lysosomal glycohydrolases in human tonsil B lymphocytes (TBL) undergoing in vitro spontaneous apoptosis. Fluorimetric methods were used to evaluate the activities of beta-hexosaminidases, alpha-mannosidase, beta-mannosidase, alpha-galactosidase, beta-glucuronidase and alpha-fucosidase. Results show that in TBL during spontaneous apoptosis, there is a significant increase in the activity of beta-hexosaminidases, alpha-mannosidase, beta-mannosidase and beta-galactosidase. Also beta-glucuronidase and alpha-fucosidase activities increase but not in a significant manner. Further studies on beta-hexosaminidases revealed that also mRNA expression of the alpha- and beta-subunits, which constitute these enzymes, increases during spontaneous TBL apoptosis. When TBL are protected from apoptosis by the thiol molecule N-acetyl-L-cysteine (NAC), there is no longer any increase in glycohydrolase activities and mRNA expression of beta-hexosaminidase alpha- and beta-subunits. This study demonstrates for the first time that the activities and expression of some lysosomal glycohydrolases are enhanced in TBL during spontaneous apoptosis and that these increases are prevented when TBL apoptosis is inhibited.
Assuntos
Apoptose/fisiologia , Linfócitos B/enzimologia , Glicosídeo Hidrolases/fisiologia , Lisossomos/enzimologia , Células Cultivadas , HumanosRESUMO
PURPOSE: This study was done to analyse the additional morphological and functional information provided by the integration of [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography ([18F]-FDG-PET) with contrast-enhanced multidetector computed tomography (MDCT) in the characterisation of indeterminate solitary pulmonary nodules (SPNs). MATERIALS AND METHODS: Fifty-six SPNs, previously classified as indeterminate, were evaluated using a Discovery ST16 PET/CT system (GE Medical Systems) with nonionic iodinated contrast material and [18F]-FDG as a positron emitter. Images were evaluated on a dedicated workstation. Semiquantitative parameters of [18F]-FDG uptake and morphological, volumetric and densitometric parameters before and after contrast administration were analysed. Results were correlated with the histological and follow-up findings. RESULTS: Twenty-six SPNs were malignant and 30 were benign. Malignant lesions at both PET/CT and histology had a mean diameter of 1.8+/-1.2 cm, a volume doubling time (DT) of 222 days, a mean standardized uptake value (SUV) of 4.7 versus 1.08 in benign lesions and a mean postcontrast enhancement of 44.8 HU as opposed to 4.8 HU in benign nodules. Malignant lesions had a significantly shorter doubling time and significantly greater postcontrast enhancement compared with benign nodules. Based on the SUV and using a cut-off value of >2.5, PET/CT had a sensitivity of 76.9%, specificity of 100%, diagnostic accuracy of 89.2%, positive predictive value (PPV) of 100% and negative predictive value (NPV) of 83.3%. Based on doubling time (cut off<400 days), it had a sensitivity of 76.9%, specificity of 93.3%, accuracy of 85.7%, PPV of 90.9% and NPV of 82.3%. Based on postcontrast enhancement (cut off>15 HU), it had a sensitivity of 92.3%, specificity of 100%, accuracy of 96.4%, PPV of 100% and NPV of 93.7%. CONCLUSION: PET/CT allows accurate analysis of anatomical/morphological and metabolic/functional correlations of SPN, providing useful data for identifying and locating the disease, for differentiating between malignant and benign nodules and for establishing the aggressiveness and degree of vascularity of pulmonary lesions. Therefore, partly in view of the considerable reduction in time and cost of the single examinations, we believe that PET/CT will gain an increasingly dominant role in the diagnostic and therapeutic approach to lung cancer, especially in the preclinical phase.