RESUMO
Human papillomavirus (HPV) is considered to be one of the viral infections associated with cancers and other diseases. HPV is detected asymptomatically in the oral mucosa. The presence of human papillomavirus in the oral mucosa appears to be closely associated with a series of benign and malign oral lesions. The aim of this paper is to report the Italian experience in applying translational protocols, using new technologies and multidisciplinary strategies in Human Papilloma virus detection and treatment. The "HPV board: a future without papilloma virus" project was born, promoted by CNEL (Italian Council of Economics and Labor) with the collaboration of numerous scientific societies to commonly approach to public knowledge of HPV-related oral lesions and their clinical management. The preliminary results are related to the assessment of the proof-of-concept of this new project. More in details, "HPV Board" is a project that plans the presence of a working group, made up of otolaryngologists, dentists, oral and maxillofacial surgeons, in close contact with gynecologists, oncologists and pediatricians; this working group manages to combine very transversal skills, in order to promote primary prevention projects, early diagnosis and adequate therapies. The "HPV BOARD" project will give the opportunity to increase the attention of patients and doctors on the early diagnosis of oncological diseases dependent on infection by the infectious agent HPV. In this panorama, dentists will have the role of "first sentinel" of public health because oral health is an indicator, too often overlooked, for the prevention of numerous diseases.
Assuntos
Papiloma , Infecções por Papillomavirus , Humanos , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Papillomaviridae , ItáliaRESUMO
SUMMARY: The objective of this work is to evaluate the safety, feasibility and efficacy of trans-nasal fiberendoscopic injection laryngoplasty (IL) with centrifuged autologous fat, performed under local anaesthesia, in the treatment of glottic insufficiency due to unilateral vocal fold paralysis (UVFP). It is a within-subject study with follow-up 1 week after phonosurgery and after 6 months. A total of 22 patients with chronic dysphonia caused by glottic insufficiency due to UVFP were enrolled. Each patient underwent trans-nasal IL with centrifuged autologous fat through flexible operative endoscope under local anaesthesia and was evaluated before and twice (1 week and 6 months) after phonosurgery, using a multidimensional set of investigations. The assessment protocol included videolaryngostroboscopy, perceptual evaluation of dysphonia, maximum phonation time and patient's self-assessment on voice-related quality of life (QOL) with the Voice Handicap Index-10 and the comparative self-assessment on vocal fatigue and voice quality pre-post treatment. Trans-nasal IL with centrifuged autologous fat was performed in all 22 patients and there were no complications in any case. Significant improvements in videolaryngostroboscopic findings, perceptual evaluation of dysphonia, maximum phonation time and QoL self-assessment were reported after 1 week and were maintained at 6 months. In one patient, the result after 6 months was not satisfactory and this patient then underwent a medialization laryngoplasty (thyroplasty type I) with satisfactory long-term results. In conclusion, trans-nasal fiberendoscopic IL with centrifuged autologous fat seems to be a safe, feasible and efficacious phonosurgical procedure for treatment of glottic insufficiency due to unilateral vocal fold paralysis.
Assuntos
Tecido Adiposo/transplante , Glote , Doenças da Laringe/etiologia , Doenças da Laringe/cirurgia , Laringoplastia , Laringoscopia , Paralisia das Pregas Vocais/complicações , Adulto , Idoso , Centrifugação , Estudos de Viabilidade , Feminino , Tecnologia de Fibra Óptica , Humanos , Injeções , Laringoplastia/efeitos adversos , Laringoplastia/métodos , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural , Nariz , Resultado do TratamentoRESUMO
Chronic inflammation is often accompanied by angiogenesis, the development of new blood vessels from existing ones. This vascular response is a response to chronic hypoxia and/or ischemia, but is also contributory to the progression of disorders including atherosclerosis, arthritis, and tumor growth. Proinflammatory and proangiogenic mediators and signaling pathways form a complex and interrelated network in these conditions, and many factors exert multiple effects. Inflammation drives angiogenesis by direct and indirect mechanisms, promoting endothelial proliferation, migration, and vessel sprouting, but also by mediating extracellular matrix remodeling and release of sequestered growth factors, and recruitment of proangiogenic leukocyte subsets. The role of inflammation in promoting angiogenesis is well documented, but by facilitating greater infiltration of leukocytes and plasma proteins into inflamed tissues, angiogenesis can also propagate chronic inflammation. This review examines the mutually supportive relationship between angiogenesis and inflammation, and considers how these interactions might be exploited to promote resolution of chronic inflammatory or angiogenic disorders.
Assuntos
Inflamação , Neovascularização Patológica/imunologia , Transdução de Sinais , Remodelação Vascular/imunologia , Animais , Feminino , Humanos , Masculino , Neovascularização Patológica/metabolismoRESUMO
Angiogenesis is a feature of numerous pathologies including cancer and inflammatory conditions and as such is key therapeutic target for the treatment of disorders where excessive or insufficient formation of new blood vessels occurs. The study of angiogenesis in vivo provides many challenges, however the growth of new blood vessels in vitro from aortic explants has provided a highly useful model for the study of this process. In this manuscript we examine the critical factors which can affect this assay and demonstrate that aortas from both female rats and mice exhibit a reduced angiogenic response to males. These findings have implications not only for the experimental design of angiogenesis experiments but also in the use of therapies targeting angiogenesis in the treatment of pathologies, such as cancer.
RESUMO
We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)-L-asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Irradiação Craniana , Feminino , Seguimentos , Hematologia/organização & administração , Humanos , Lactente , Itália , Masculino , Oncologia/organização & administração , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Prognóstico , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
The pathogenesis of infant acute lymphoblastic leukemia (ALL) is still not well defined. Short latency to leukemia and very high concordance rate for ALL in Mixed-Lineage Leukemia (MLL)-positive infant twins suggest that the MLL rearrangement itself could be sufficient for overt leukemia. Attempts to generate a suitable mouse model for MLL-AF4-positive ALL did not thoroughly resolve the issue of whether cooperating mutations are required to reduce latency and to generate overt leukemia in vivo. In this study, we applied single-nucleotide polymorphism array technology to perform genomic profiling of 28 infant ALL cases carrying t(4;11) to detect MLL-cooperating aberrations hidden to conventional techniques and to gain new insights into infant ALL pathogenesis. In contrast to pediatric, adolescent and adult ALL cases, the MLL rearrangement in infant ALL is associated with an exceptionally low frequency of copy-number abnormalities, thus confirming the unique nature of this disease. By contrast, additional genetic aberrations are acquired at disease relapse. Small-segmental uniparental disomy traits were frequently detected, mostly constitutional, and widely distributed throughout the genome. It can be argued that the MLL rearrangement as a first hit, rather than inducing the acquisition of additional genetic lesions, has a major role to drive and hasten the onset of leukemia.
Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Dosagem de Genes , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Feminino , Humanos , Lactente , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Single photon emission tomography was used to map blood flow increase in temporal and parietal cortex after auditory stimulation in 25 subjects: 10 normal-hearing, 10 severe-profound hearing-impaired and 5 totally deaf. After a 500 Hz pure tone stimulation, a marked perfusion increase was observed, particularly at the level of the contralateral auditory temporal cortex. Blood flow increase in temporal and parietal cortical areas of normal subjects was significantly higher than that observed in severe-to-profound hearing-impaired patients. In all cases, following 500 Hz pure tone acoustic stimulation, the most lateral sagittal slice tomograms (48.75 and 56.25 mm) showed the highest blood flow increase. Statistically significant differences were also observed between normal subjects and hearing-impaired patients in the 48.75 mm sagittal tomogram. In 2 hearing-impaired patients, the single photon emission tomography pattern showed activation of the intermediate sagittal tomogram, suggesting a possible new tonotopic cortical arrangement. No significant activation was present in totally deaf patients. In conclusion, Single Photon Emission Tomography appears to be a useful tool in the evaluation of auditory cortical activation and cortical plasticity, in severe-to-profound hearing-impaired patients. Moreover, it could be a useful test for the study of auditory central pathways.
Assuntos
Estimulação Acústica/métodos , Surdez/diagnóstico por imagem , Perda Auditiva Neurossensorial/diagnóstico por imagem , Lobo Parietal/irrigação sanguínea , Lobo Parietal/diagnóstico por imagem , Lobo Temporal/irrigação sanguínea , Lobo Temporal/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Audiometria de Tons Puros , Vias Auditivas/diagnóstico por imagem , Limiar Auditivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaAssuntos
Resistencia a Medicamentos Antineoplásicos/genética , Fatores Inibidores da Migração de Macrófagos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prednisona/farmacologia , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Although therapeutical advances have been achieved, some ALL subgroups still fare poorly. CD1d is a monomorphic molecule that provides a suitable target for immunotherapy in view of the characterization of a glycolipid, alpha-galactosylceramide (alpha-GalCer), capable of being presented to CD1d-restricted T cells with cytotoxic potential. We investigated CD1d expression in 80 pediatric B-cell precursor (BCP) ALL cases defined according to immunophenotype, cytogenetic features and age at onset. CD1d was detected on ALL cells in 15% of the patients. CD1d+ ALLs were significantly associated with infant leukemia, pro-B phenotype and mixed-lineage leukemia (MLL)/AF4 gene rearrangement. Accordingly, overall survival of patients with CD1d+ ALL was significantly shorter. CD1d+ leukemic blasts were able to present alpha-GalCer via CD1d to cytotoxic CD1d-restricted T cells, which induced apoptosis of ALL cells that was inhibited by mAb to CD1d. CD1d+ blasts loaded with alpha-GalCer elicited cytokine secretion by CD1d-restricted T cells. Analysis of bone marrow (BM) cells derived from normal donors revealed that CD19+/CD1d+ cells were mostly mature B lymphocytes. However, a minority of BCPs expressed CD1d. Thus, expression of CD1d in ALL cases heralds an adverse prognosis but may provide a therapeutic tool.
Assuntos
Antígenos CD1/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Antígenos CD1d , Linfócitos B/citologia , Biomarcadores Tumorais/metabolismo , Comunicação Celular , Linhagem Celular , Criança , Galactosilceramidas/metabolismo , Células-Tronco Hematopoéticas/citologia , Humanos , Lactente , Células Matadoras Naturais/citologia , Células Matadoras Naturais/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Valor Preditivo dos Testes , Prognóstico , Taxa de SobrevidaRESUMO
NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.
Assuntos
Proteínas de Ligação a DNA/genética , Rearranjo Gênico , NAD(P)H Desidrogenase (Quinona)/genética , Polimorfismo Genético/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes/genética , Fatores de Transcrição/genética , Regulação Neoplásica da Expressão Gênica/genética , Genótipo , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Proteína de Leucina Linfoide-Mieloide , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Valores de ReferênciaRESUMO
From July 1995 to December 2001, 42 patients with leukemia aged 1-42 years underwent cord blood transplant (CBT) from unrelated, < or = 2 antigen HLA mismatched donors. In all, 26 patients were in < or = 2nd complete remission and 16 in more advanced phase. Conditioning regimens, graft-versus-host disease (GVHD) prophylaxis and supportive policy were uniform for all patients. The cumulative incidence of engraftment was 90% (95% CI: 0.78-0.91). The cumulative incidence of III-IV grade acute- and chronic-GVHD was 9% (95% CI: 0.04-0.24) and 35% (95% CI: 0.21-0.60), respectively. The 4-year cumulative incidence of transplant-related mortality (TRM) and relapse was 28% (95% CI: 0.17-0.47) and 25% (95% CI: 0.14-0.45), respectively. The 4-year overall survival (OS), leukemia-free survival (LFS) and event-free survival (EFS) were 45% (95% CI: 0.27-0.63), 47% (95% CI: 0.30-0.64) and 46% (95% CI: 0.30-0.62), respectively. In multivariate analysis, the most important factor affecting outcomes was the CFU-GM dose, associated with CMV serology (P=0.003 and 0.04, respectively) in influencing OS and with patient sex (P=0.008 and 0.03, respectively) in influencing LFS. Finally, CFU-GM dose was the only factor that affected EFS significantly (P=0.02). In conclusion, the infused cell dose expressed as in vitro progenitor cell growth is highly predictive of outcomes after an unrelated CBT and should be considered the main parameter in selecting cord blood units for transplant.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/estatística & dados numéricos , Leucemia/terapia , Adolescente , Adulto , Contagem de Células , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Células-Tronco Hematopoéticas/citologia , Humanos , Lactente , Leucemia/diagnóstico , Leucemia/mortalidade , Estudos Longitudinais , Masculino , Prognóstico , Fatores de Risco , Análise de Sobrevida , Doadores de Tecidos , Resultado do TratamentoRESUMO
Activation of the auditory cortex by multifrequency acoustic stimuli has been evaluated using Single Photon Emission Tomography in a case of auditory brainstem implant after activation of 6 and 11 electrodes. Before implantation, no activation of the auditory cortex has been observed after acoustic stimulation. Following auditory brainstem implant, the stimulation of 11 electrodes showed an activation value, in terms of blood flow increase, of the contralateral temporal cortex similar to that obtained with 6 electrodes (47.70 vs. 43.76%), but a significantly stronger activation was present in the contralateral parietal region (29.59 vs. 14.73%), in the homolateral temporal area (22.02 vs. 10.46%) and, especially, in the homolateral parietal zone (16.6 vs. 4.33%). The strongest activation in the contralateral temporal cortex was detected in the sagittal tomogram at 26.25 mm from the midline, that is in the areas where high frequencies are projected, both with 6 and 11 active electrodes. The medio-lateral auditory cortex, where the middle and lower frequencies are projected, showed an overall lower activation which was however significantly lower with 6-electrode stimulation. Stimulation of the surface of cochlear nuclei determines mainly an activation of the high frequency domain, independently of the electrodes number. This finding may explain the better results of cochlear implants in comparison with auditory brainstem implant and could justify the use of needle electrodes in auditory brainstem implant. In conclusion, Single Photon Emission Tomography can be considered useful in evaluating auditory brainstem implant placement and function. It is also able to define the effectiveness of acoustic stimulation, the degree and tonotopic spatial distribution of auditory cortex activation.
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Estimulação Acústica/instrumentação , Córtex Auditivo/irrigação sanguínea , Tronco Encefálico/cirurgia , Implantação de Prótese , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Surdez/etiologia , Surdez/cirurgia , Eletrofisiologia/instrumentação , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Humanos , Masculino , Neurofibromatose 2/complicações , Neurofibromatose 2/cirurgia , Lobo Parietal/fisiologiaAssuntos
Neoplasias Encefálicas/diagnóstico por imagem , Tumor do Glomo Jugular/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Tálio , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Veias Cerebrais/diagnóstico por imagem , Tumor do Glomo Jugular/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Lobo Temporal/patologia , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
A child with AML underwent allogeneic BMT from an HLA-identical sister donor. Prompt and stable triline-age engraftment occurred and after few months he returned to a normal life. Eight years later a primary NHL of bone developed in his sister. A partial remission was obtained by means of standard NHL treatment, but 3 months later rapid disease progression occurred with complete bone marrow invasion (ALL-L3). She was treated with a leukemia relapse protocol, obtaining a second partial remission. Unpurged bone marrow harvested from the brother, transplanted for AML 8 years earlier, was infused after conditioning with TBI and thiothepa. No GVHD prophylaxis was given. Neutrophil engraftment occurred by 14 days and platelet engraftment by 20 days after BMT. No acute GVHD was observed, but unexpectedly she developed skin and liver GVHD-like symptoms 80 days after BMT. Since the liver biopsy was suggestive of liver GVHD and in the absence of any other evidence as a possible cause of the hepatic damage, the patient started mycophenolate. Two months later serum hepatitis B markers were detectable.
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Transplante de Medula Óssea/métodos , Adolescente , Transplante de Medula Óssea/efeitos adversos , Linfoma de Burkitt/terapia , Criança , Feminino , Doença Enxerto-Hospedeiro/etiologia , Hepatite B/etiologia , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Irmãos , Transplante Homólogo , Transplante IsogênicoRESUMO
BACKGROUND AND OBJECTIVES: In March 1987 AIEOP started the AIEOP-ALL-87 study, based on the previous AIEOP-ALL-82. The aim of this new study was to evaluate, for all risk groups: a) the efficacy of treatment intensification achieved by adding a fourth drug (daunomycin) in the induction phase and a 3-drug reinduction phase for all risk groups; b) the impact of the addition of three doses of intrathecal methotrexate during cranial radiotherapy and extended exposure to weekly high-dose L-aspariginase during late intensification in high risk patients. We report the long-term results of the AIEOP ALL-87 study. DESIGN AND METHODS: From 1987 to 1991, a total of 632 eligible and evaluable children (age 1 to < or =16 years) with non-B-cell acute lymphoblastic leukemia (ALL), were enrolled and stratified as follows: standard risk (SR, 79 patients, 12.5%) had WBC <10,000/mm3, age > or = 3 and <7 years, and FAB L1 morphology. The high risk (HR, 175 patients, 27.7%) group included patients with WBC > or =50,000/mm3 or FAB L3 morphology or T immunophenotype or acute undifferentiated leukemia (AUL) or leukemia-lymphoma syndrome. All the remaining patients formed the intermediate risk group (IR, 378 patients, 59.8%). All patients received a 4-drug induction therapy; intermediate-dose methotrexate was given to HR patients; cranial radiotherapy was given to IR and HR patients, while SR patients received extended intrathecal methotrexate; all patients received a 3-drug reinduction phase; high dose L-asparaginase (HD-L-ASP; E.Coli, Bayer) was given to HR patients; continuation therapy with 6-mercaptopurine, i.m. methotrexate, and monthly vincristine and prednisone pulses was given to all patients. Treatment duration was 2 years. RESULTS: Six hundred and nineteen patients (97.9%) achieved complete remission. The remission rate was 98.7% in the SR group, 98.1% in the IR group, and 97.1% in the HR group. The overall 10-year survival and event-free survival (EFS) rates (SE) are 74.7% (1.8) and 62.8% (2.0) respectively; EFS rates by risk group are 67.5% (5.5) in SR, 62.8% (2.6) in IR, and 61.9% (3.8) for HR. The 10-year EFS for all eligible patients was 63.9% (1.9). INTERPRETATION AND CONCLUSIONS: When compared to the results of the AIEOP-ALL-82 study, treatment intensification in the ALL-87 study has improved long-term survival and EFS from 66.4% and 53.6% to 74.7% and 62.8%, respectively. Failures were mostly due to marrow or extramedullary relapses suggesting that further treatment intensification, as being used in current therapeutic strategies, is appropriate, although patients relapsing after less intensive treatment may have better chances of rescue. These results, although obtained in a relatively large proportion of patients, in which infants were not included, indicate that the addition of high-dose L-asparaginase to a relatively non-intensive treatment may be of major benefit for HR patients and that the addition of intrathecal methotrexate during CRT, may improve the central nervous system-disease control with a marked reduction of nervous system relapses.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Asparaginase/administração & dosagem , Criança , Pré-Escolar , Daunorrubicina/administração & dosagem , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Prednisona/administração & dosagem , Prognóstico , Indução de Remissão , Fatores de Risco , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
In view of the relevance of adhesion molecule expression for the mechanisms of homing, trafficking and spreading of malignant cells, we have investigated the expression of surface adhesion molecules in lymphoblasts from 57 acute lymphoblastic leukemia (ALL) cases and tried to correlate the adhesive phenotype with immunological typing, prognostic factors at diagnosis and clinical follow-up. Blasts from all cases expressed adhesion molecules at high rates. Beta1 integrin chain (CD18) was consistently found on blasts from most ALL cases: among integrins of the beta2 family. LFA-1 was detected in 58% of cases, in the virtual absence of other alpha chains. CD54 and CD58 were expressed in variable proportions by ALL blasts and CD44 was detected in the majority of the malignant cells, whereas the CD62L selectin was only present in 24% of cases. B-lineage ALL's displayed similar adhesion molecule phenotypes irrespective of maturational stages of the leukemic cells. We found a significantly reduced expression of beta2 alphaL integrins in the hybrid ALL cases (CD13 and/or CD33 positive). However, these cases did not show differences in clinical presentation and behaviour in comparison with patients of other groups. We did not find a significant correlation between adhesion molecule expression and well established risk factors (age, white blood cell count, central nervous system involvement, chromosomal abnormalities), with the exception of splenomegaly, that was significantly associated with CD18 expression. In the follow-up, no evidence of significant correlation between adhesive phenotype and adverse events such as leukemic relapse and death was found. In conclusion, although expression of adhesion molecules on lymphoblasts confirms the phenotypic heterogeneity of ALL, it appears that this is not relevant for the clinical aspects of the disease and for prognosis.
Assuntos
Moléculas de Adesão Celular/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Adolescente , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Adesão Celular , Moléculas de Adesão Celular/efeitos dos fármacos , Criança , Pré-Escolar , Humanos , Lactente , Invasividade Neoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologiaRESUMO
OBJECTIVES: Patients with Alzheimer's disease (AD) showing a selective impairment of episodic and semantic memory have recently been classified as affected by focal temporal lobe dysfunction (FTLD) and considered as a distinct subgroup of patients affected by a particular form of AD. The aim was to compare the cerebral perfusion of patients with AD with FTLD and patients with AD with the more typical profile of diffuse cognitive impairment (dAD). METHODS: Ten patients with AD with FTLD, 14 patients with AD with dAD, and 12 normal controls were studied. All the 24 patients with AD underwent a complete neuropsychological assessment. SPECT examination with [(99m)Tc]-HMPAO, using a four head brain dedicated tomograph, was performed in patients and controls. Tracer uptake was quantified in 27 regions of interest (ROIs), including lateral and mesial temporal areas. Mean counts in the 27 ROIs of controls, patients with FTLD and those with dAD were compared using an ANOVA for repeated measures with Bonferroni's correction. A logistic regression analysis, followed by a receiver operating characteristic (ROC) analysis, was also applied to select SPECT patterns which significantly differentiated patients with FTLD and those with dAD. RESULTS: Two scintigraphic patterns of abnormalities, shaping a double dissociation between the FTLD and dAD groups, emerged: a bilateral mesial temporal hypoperfusion, characteristic of FTLD and a posterior parietal (and temporal parietal) hypoperfusion characteristic of patients with dAD. CONCLUSIONS: These scintigraphic findings provide further support to the hypothesis that FTLD is not a mere stage but a distinct anatomoclinical form of AD. The combination of neuropsychological tests and [(99m)Tc]-HMPAO SPECT may be very useful in identifying patients with FTLD from the wider group of patients with dAD. This issue is particularly worthwhile, as there is increasing evidence that patients with FTLD have a slower rate of cognitive decline.
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Doença de Alzheimer/fisiopatologia , Circulação Cerebrovascular/fisiologia , Transtornos Cognitivos/fisiopatologia , Lobo Temporal/fisiopatologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Análise de Variância , Transtornos Cognitivos/diagnóstico por imagem , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Lobo Temporal/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Auditory cortex activation following multifrequency acoustic stimulation has been evaluated by means of single photon emission tomography (SPET) in one patient before and after an auditory brainstem implant (ABI). No activation could be observed after acoustic stimulation before ABI. After ABI stimulation in the coronal and axial slices, the activation within the temporal cortex contralateral to the stimulated ear was twice (43.76%) that of normal controls (23.94 +/- 2.74%). This marked difference was not present in other selected cortical auditory areas (homolateral temporal, homolateral and contralateral parietal cortices). The temporal cortex was also examined with six consecutive sagittal slices from 18.75 mm up to 56.25 mm lateral to the midline. A very strong activation (51.20%) compared with that of normal controls (9.94 +/- 7.45%) was detected in the 25.26-mm sagittal slice of the temporal cortex contralateral to the stimulated side. The remaining sagittal slices showed an almost normal post-stimulatory activation. As the 25.26-mm sagittal slice corresponds to the medial part of the auditory temporal cortex, its activation suggests that electrode stimulation is concentrated on the region of the cochlear nucleus in which the neurons that transduce high frequencies are located. SPET can be considered useful, in combination with electric auditory-evoked potentials, to obtain information on ABI placement and function, effectiveness of acoustic stimulation, degree of cortical stimulation and tonotopic spatial distribution of auditory cortex activation.
Assuntos
Córtex Auditivo , Doenças Auditivas Centrais/cirurgia , Implantes Cocleares , Estimulação Elétrica/métodos , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Doenças Auditivas Centrais/etiologia , Estimulação Elétrica/instrumentação , Humanos , Masculino , Monitorização Fisiológica , Neurofibromatose 2/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversosRESUMO
Few articles on neuroimaging techniques in the study of central and peripheral olfactory pathways are present in the literature. By Single Photon Emission Computed Tomography (SPECT), cortical perfusion increment after sensorial stimulation can be evaluated objectively. In the present research, 10 healthy adults underwent SPECT by CER.TO.96 cerebral tomograph, before and after olfactory stimulation with lavender-water. A variable degree of cortical activation was detected in all patients. Gyrus rectus (+24.5%), orbito-frontal cortex (right +26.6%, left +25.6%), and superior temporal (right +9.9%, left +5.5%) cortical areas were always activated. A slight perfusion increase was present in middle temporal (right +3.2%, left +2.1%) and parieto-occipital (right +0.4%, left +2%) regions. Five patients affected by posttraumatic anosmia were also investigated: they showed a perfusion increment markedly inferior to 0.5% in every olfactory area. SPECT is a rather diffused, easily performed technique which yields objective semi-quantitative information on brain perfusion. Hence, it can be regarded as a promising contribution in the fields of smell neurophysiology, clinical olfactometry, and medicolegal queries.
Assuntos
Condutos Olfatórios/diagnóstico por imagem , Olfato/fisiologia , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurofisiologia , Condutos Olfatórios/fisiologia , Tomografia Computadorizada de EmissãoRESUMO
PURPOSE: This was a radioisotope study of nasal mucociliary clearance of total and subtotal nasal obstruction. METHODS: Rhinoscintigraphy was performed by insufflating 1.85 MBq (69 mCi) Tc-99m MAA in 20 patients. Six cases were regarded as the control group, because the presence of small spurs does not affect nasal patency. The remaining 14 patients had various rhinopathic conditions. Two regions of interest were selected, one in the nasal cavity and one in the pharynx. Mucociliary transport speed was calculated. RESULTS: This parameter appeared to be a sensitive index for the assessment of the degree of mucociliary alteration. It showed that polyposis impairs mucociliary transport most severely, thus confirming the results of other published studies. CONCLUSIONS: Rhinoscintigraphy proved to be a reliable, easily reproducible, and harmless method, so it may be used for follow-up examinations in patients who have had surgery of the nose and paranasal sinuses, and for drug therapy of rhinopathic conditions.