RESUMO
BACKGROUND: We prospectively analyzed the effect of preexisting structural changes of the radial artery (RA) wall by histological examination on the wrist radiocephalic fistula (RCF) outcomes. METHODS: During RCF creation, one segment of the RA wall was collected and its histomorphometric analysis was performed. The RCF function was evaluated by measuring blood flow rate. RESULTS: At the end of follow-up, 75.7% of the thirty-seven patients enrolled were performing hemodialysis by using their successful RCF and 24.3% of them showed early RCF failure. Compared to patients with a healthy RA, the RCF of those with medial RA microcalcification reached up a lower flow and a shorter primary patency (P=0.005 and P=0.040, respectively). The RA microcalcification was predictive of the RCF function (coefficient -614.9, 95% CI: -994.7 to -235.1, P=0.003). Compared to patients with successful RCF, those with failed RCF had a greater frequency of weak RCF thrill after releasing the clamps (P=0.045). Dependence on hemodialysis during RCF placement was predictive of its early failure (OR: 23.2, 95% CI: 1.76 to 306.9, P=0.017). Both having at least one cardiovascular comorbidity (HR 4.30, 95% CI: 1.29 to 14.39, P=0.018) and a thicker media layer of the RA (HR 1.60, 95% CI: 1.87 to 2.15, P=0.002) were predictive of primary RCF patency. CONCLUSIONS: The function and survival of the successful RCF were related to preoperative RA abnormalities such as microcalcification and media layer thickness. Both dependence on hemodialysis during RCF placement and an attenuated RCF thrill were associated with early RCF failure.
Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Oclusão de Enxerto Vascular/etiologia , Esclerose Calcificante da Média de Monckeberg/complicações , Artéria Radial/patologia , Extremidade Superior/irrigação sanguínea , Grau de Desobstrução Vascular , Idoso , Idoso de 80 Anos ou mais , Feminino , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Calcificante da Média de Monckeberg/fisiopatologia , Análise Multivariada , Estudos Prospectivos , Artéria Radial/cirurgia , Radiografia , Análise de Regressão , Diálise Renal , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , UltrassonografiaRESUMO
AIMS: In T cells, protein kinase C (PKC) theta plays a major role in T-cell receptor (TCR)-mediated activation of a novel nuclear factor (NF)-kappaB pathway that involves phosphorylation of p65 at serine 536 (Pp65(Ser536)). Bcl-10 acts along the same pathway downstream of PKC theta to activate NF-kappaB. The aim was to investigate the relationship between the expression of PKC theta, Bcl-10 and P-p65(Ser536) proteins and their prognostic significance in peripheral T-cell lymphomas (PTCLs). METHODS AND RESULTS: Paraffin-embedded tissues from 30 patients with PTCLs treated with curative intention were evaluated retrospectively. Expression of PKC theta, Bcl-10 and P-p65(Ser536) proteins was assessed using immunohistochemistry. Expression of PKC theta was detected in 22 of 30 cases (73%), Bcl-10 in 20 of 30 (67%) and P-p65(Ser536) in 21 of 30 (70%). Bcl-10+ tumours were associated with PKC theta (18 of 22) (P < 0.0001) and Pp65Ser536 (19 of 21) expression (P < 0.0001). Patients with Bcl-10+ or P-p65(Ser536+) tumours fared better, with a 5-year overall survival of 48 and 45%, respectively, versus 0% for negative tumours (P = 0.029 and P = 0.04, respectively). CONCLUSIONS: Bcl-10 is expressed in PTCLs, correlates with PKC theta and Pp65(Ser536) expression and seems to be associated with better survival.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/patologia , Fator de Transcrição RelA/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína 10 de Linfoma CCL de Células B , Feminino , Humanos , Imuno-Histoquímica , Isoenzimas/metabolismo , Masculino , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Proteína Quinase C/metabolismo , Proteína Quinase C-theta , Estudos Retrospectivos , Serina/química , Taxa de Sobrevida , Análise Serial de Tecidos , Fator de Transcrição RelA/química , Adulto JovemRESUMO
BACKGROUND: Monitoring of post-transplant heart rejection is currently based on endomyocardial biopsy analysis. This study aimed to assess the effects of heart graft rejection on myocardial electrical impedance. METHODS AND RESULTS: Twenty-nine cardiac transplant patients and 9 controls underwent measurement of myocardial electrical impedance using a specifically designed amplifying system. The module and phase angle of myocardial impedance were measured. Histopathological rejection grading was performed according to ISHLT classification. Fifty impedance tests were performed in transplanted patients. Myocardial impedance (Z) was higher in controls than in transplanted patients (p<0.001) and followed a progressive decline at increasing current frequencies (p<0.001). Likewise, the phase angle of impedance in controls ranged from positive values at low frequencies to negative values at higher frequencies (from 2.5+/-0.9 degrees at 10 kHz to -3.8+/-2.1 degrees at 300 kHz, p<0.001). Rejection was associated with a significant decrease in myocardial impedance (Z) (15+/-6.6 Omega in grade 0, 13+/-6.0 Omega in grade 1A, and 3.3+/-0.9 Omega in grade 3A at 10 kHz, p<0.003). CONCLUSIONS: Mild degrees of cardiac graft rejection are associated with significant changes in myocardial electrical impedance in transplant patients. Further clinical investigation is warranted to assess the potential of cardiac impedance to detect heart graft rejection.
Assuntos
Impedância Elétrica , Técnicas Eletrofisiológicas Cardíacas/métodos , Rejeição de Enxerto/diagnóstico , Transplante de Coração , Processamento de Sinais Assistido por Computador , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Fatores de TempoRESUMO
The protein kinase C (PKC) plays an important role in the activation and survival of B cells. The purpose of this study was to analyze the clinical significance of PKC-beta 2 protein expression in patients with diffuse large B-cell lymphoma (DLBCL). Tumors from 76 patients with DLBCL who received anthracycline-containing chemotherapy were examined for PKC-beta 2 protein expression by immunohistochemistry. Twenty-six cases (34%) were positive for PKC-beta 2 protein, and 50 (66%) were negative. Patients with PKC-beta-2-positive tumors showed a lower complete remission rate (31 vs 62%; P=0.015) and a lower 5-year disease-free survival (DFS) (30 vs 60%; P=0.03) than the PKC-beta-2-negative group. Overall survival (OS) was significantly lower in patients with the membranous staining pattern of PKC-beta 2 protein when compared to those with PKC-beta-2-negative tumors (14 vs 64%; P=0.005). In patients with low international prognostic index (IPI), those with tumors showing membrane expression of PKC-beta 2 had a significantly inferior DFS and OS (0 vs 79%, P=0.003; 25 vs 80%; P=0.01) compared to PKC-beta-2-negative tumors. In multivariate analysis for OS, the membrane staining of PKC-beta 2 is the strongest independent adverse prognostic factor (OR=3.4, P=0.011). Our results suggest that membrane expression of PKC-beta 2 protein on DLBCL predicts for poor survival, especially in patients with low IPI.
Assuntos
Biomarcadores Tumorais/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Linfoma de Células B/enzimologia , Linfoma Difuso de Grandes Células B/enzimologia , Proteínas de Neoplasias/biossíntese , Proteína Quinase C/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/genética , Membrana Celular/enzimologia , Membrana Celular/genética , Criança , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/genética , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/genética , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Valor Preditivo dos Testes , Prednisona/administração & dosagem , Proteína Quinase C/genética , Proteína Quinase C beta , Estudos Retrospectivos , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal lung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis.
Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Fumar/efeitos adversos , Fumar/patologia , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/patologia , Humanos , Doenças Pulmonares Intersticiais/etiologia , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
No disponible
Assuntos
Masculino , Pessoa de Meia-Idade , Humanos , Carcinoma/complicações , Carcinoma/diagnóstico , Carcinoma/cirurgia , Lipoma/complicações , Lipoma/diagnóstico , Lipoma/cirurgia , Glândulas Perianais/patologia , Glândulas Perianais/cirurgia , Neoplasias das Glândulas Anais/complicações , Neoplasias das Glândulas Anais/diagnóstico , Carcinoma/patologia , Carcinoma/fisiopatologia , Cirurgia Colorretal/métodos , Reto/patologia , Reto/cirurgia , Reto , Neoplasias Retais/cirurgia , Neoplasias RetaisRESUMO
Epithelioid granuloma formation has rarely been observed in specific cutaneous lesions from T-cell lymphomas other than those of mycosis fungoides/Sézary syndrome (MF/SS). Three patients diagnosed with nodal and/or extranodal (tonsillar) non-Hodgkin's peripheral T-cell lymphoma (PTCL) and one patient with angioimmunoblastic T-cell lymphoma (AILD), developed specific cutaneous involvement showing prominent epithelioid cell and/or granulomatous inflammation. The original diagnostic lesions had no granulomatous features. In addition to a specific lymphomatous infiltrate, prominent dermal and/or subcutaneous granulomatous infiltrates were observed. Sarcoid-like granulomas were observed in two patients (one of them presented a granuloma annulare-like pattern in early lesions), granulomatous panniculitis was noted in one patient and in one patient with AILD, masses of epithelioid cells were noted. The clinicopathological features of cutaneous involvement by PTCL showing a florid epithelioid and/or granulomatous cell reaction are reviewed. Various histopathological patterns can be observed. The diagnostic difficulties of these cases are stressed.
Assuntos
Células Epitelioides/patologia , Granuloma/complicações , Linfoma de Células T Periférico/complicações , Dermatopatias/complicações , Idoso , Feminino , Granuloma/patologia , Humanos , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Pele/patologia , Dermatopatias/patologiaRESUMO
Oral involvement in cutaneous CD30+ T-cell lymphoid proliferations is rare and has received little attention in the dermatologic literature. The authors report 2 patients with self-healing, recurrent papulonodular eruptions with the classic clinical, histopathological and immunophenotypic features of lymphomatoid papulosis, which developed two ulcerated papules and an ulcerative nodule on the dorsum of the tongue, respectively. The lesions appeared coincident with a new cutaneous relapse of the disease. Histopathological and immunophenotypic features were similar to those of the cutaneous lesions. All lesions regressed spontaneously after several weeks. Since then, and after follow-up periods of 3 and 7 years, respectively, no evidence of extracutaneous involvement has been detected. Oral involvement in lymphomatoid papulosis is an uncommon event, probably without prognostic significance. Previously reported cases are reviewed. The differential diagnosis of atypical T-cell lymphoid infiltrates observed in the oral mucosa is discussed.
Assuntos
Papulose Linfomatoide/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Língua/diagnóstico , Diagnóstico Diferencial , Extremidades , Feminino , Humanos , Hiperlipoproteinemia Tipo IV , Ictiose , Papulose Linfomatoide/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias da Língua/secundárioRESUMO
BACKGROUND AND OBJECTIVES: Chromosome translocations resulting in gene overexpression are commonly associated with lymphoid neoplasia. Enhancer elements of the immunoglobulin or T-cell receptor (TCR) loci are abnormally located in the vicinity of the entire coding sequences of genes which exert an influence on the normal maturation and differentiation program of lymphoid cells. DESIGN AND METHODS: A patient who presented with a B-cell lineage acute lymphoblastic leukemia had a t(6;14)(p22;q32). Cytogenetic and molecular findings confirmed the involvement of IgH. Molecular cloning of the breakpoint revealed that this was located near the coding sequence of the Id4 gene, a helix-loop-helix (HLH) inhibitor protein. Alu-repeated sequences at the 6p22 end flanked a short stretch of 10 bases shared by the 6p22 and 14q32 ends, suggesting that a deletion or a looping-Alu mediated mispairing mechanism may lead to this chromosome translocation. RESULTS: Northern blot and real-time polymerase chain reaction analyses showed that the Id4 mRNA was abnormally overexpressed in this case. Only the two smaller Id4 mRNA products were detected (1.6 and 1.1 kb). Immunohistochemical analysis of Id4 protein was also assayed in a series of hematologic malignancies. Marked overexpression was found in two cases of T-cell prolymphocytic leukemias and in four B-cell lineage acute lymphoblastic leukemia including one case with the t(8;14) and another case with a p53 mutation. INTERPRETATION AND CONCLUSIONS: The Id4 gene may behave as an oncogene in some human leukemias, perhaps through its capacity to sequester specific B-cell transcription factors. A genetic recombination between Alu-repeated sequences may not be the exclusive mechanism of generating pathogenic chromosomal translocations.
Assuntos
Linfoma de Burkitt/genética , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 6/genética , Proteínas de Ligação a DNA/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Fatores de Transcrição/fisiologia , Translocação Genética/genética , Adulto , Linfoma de Burkitt/patologia , Cromossomos Humanos Par 14/fisiologia , Cromossomos Humanos Par 6/fisiologia , Proteínas de Ligação a DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Proteínas Inibidoras de Diferenciação , Fatores de Transcrição/genética , Translocação Genética/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: The t(14;18)(q32;q21) chromosomal translocation is the hallmark of follicular lymphomas (FL). The translocation induces the overexpression of the Bcl-2 protein and prolongs the survival of clonogenic cells. Tumor cells may acquire additional molecular alterations that may be associated with histologic progression or with chemo-resistance. DESIGN AND METHODS: We analyzed the distribution and association of bcl-6 and p53 mutations in 55 consecutive bcl-2/Jh+ lymphoma samples derived from 43 patients obtained at the time of diagnosis and, in 5 of these patients, during follow-up. A total of 29 bcl-6 point mutations were detected in seventeen patients (40%) associated with major or minor breakpoints of the bcl-2/Jh fusion gene. In seven cases a p53 mutation was detected. Three cases corresponded to FL with the minor breakpoint in the bcl-2 gene and these patients had a favorable clinical evolution, whereas the 4 patients with p53 mutations and the major breakpoint had a bad clinical outcome with morphologic transformation to high-grade lymphoma in three cases. The sequential analysis of 5 patients showed a different timing in the acquisition of mutations: one patient showed bcl-6 and p53 mutations at diagnosis, another patient showed bcl-6 mutations at diagnosis and acquired a p53 mutation later whereas the third patient had a p53 mutation before the appearance of the bcl-6 mutation. RESULTS: We did not find significant differences in survival between patients with FL who showed exclusively bcl-6 mutations and those without bcl-6 mutations, but those patients with a high International Progostic Index score and p53 mutations showed the lowest overall survival (p = 0.002). INTERPRETATION AND CONCLUSIONS: These findings suggest that bcl-2/Jh lymphomas show molecular heterogeneity and that bcl-6 and p53 mutations may be acquired during the evolution of such lymphomas. Bcl-6 mutations, by themselves, do not seem to be associated with a bad prognosis. Rearrangements at the minor bcl-2 locus may have a different molecular evolution.
Assuntos
Proteínas de Ligação a DNA/genética , Genes bcl-2/genética , Linfoma Folicular/genética , Mutação/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Translocação Genética/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Análise Mutacional de DNA , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6 , Taxa de SobrevidaRESUMO
We describe a 76-year-old woman who had persistent generalized pruritus as the only cutaneous manifestation of a cutaneous T-cell lymphoma (mycosis fungoides). No cutaneous lesions were observed throughout the patient's course. Skin biopsy specimens obtained from normal-looking pruritic skin revealed a discrete perivascular lymphocytic infiltrate in the upper dermis and focal intraepidermal clusters of atypical lymphoid cells (Pautrier's microabscesses). PCR analysis of TCR-gamma gene disclosed a monoclonal T-cell rearrangement. Sequencing of the PCR monoclonal product identified the J(8)V(2)C(2) TCR gene rearrangement. This observation illustrates the existence of a peculiar and exceedingly rare form of mycosis fungoides characterized only by persistent pruritus unresponsive to several therapeutic approaches. The diagnostic difficulties of this rare variant are stressed.
Assuntos
Micose Fungoide/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Feminino , Humanos , Imuno-Histoquímica , Micose Fungoide/complicações , Micose Fungoide/metabolismo , Micose Fungoide/patologia , Reação em Cadeia da Polimerase , Prurido/etiologia , Pele/patologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Patients with mature follicular B-cell lymphomas develop aggressive non-Hodgkin lymphomas (NHLs) during disease progression. It is controversial whether most diffuse large B-cell lymphomas (DLBCLs) and Burkitt lymphomas (BLs) emerge as de novo lymphomas or from an original follicular lymphoma. To distinguish clonally related populations in aggressive NHL, we studied the immunophenotypic features of 18 consecutive samples from 16 patients. Three flow cytometric patterns were distinguished: (1) a homogeneous neoplastic population of large B cells with phenotypic features of follicular center cells; (2) 2 atypical populations of B cells, small monoclonal B cells, and large B cells with loss of some surface antigens; and (3) 2 clonal populations of small and large B cells sharing the same light-chain isotype. The 3 flow cytometric patterns were observed, respectively, in de novo DLBCL and BL, transformation into BL, and transformation into DLBCL. Flow cytometric data can provide valuable information about the natural history of NHL.