RESUMO
This study investigated the effects of three different volumes of honey-thick liquid on the temporal characteristics of swallowing. Twenty-six healthy subjects (15 males, 11 females) underwent 320-row area detector CT scan while swallowing 3, 10 and 20 mL of honey-thick liquid barium. Three-dimensional images were created at 10 images/s. Kinematic events involving six structures (velopharynx, hyoid bone, epiglottis, laryngeal vestibule (LV), true vocal cords (TVC), upper esophageal sphincter (UES)) and timing of bolus movement were timed using frame by frame analysis. The overall sequence of events did not differ across three volumes; however, increasing bolus volume significantly changed the onset and termination of events. The bolus head reached to pharynx and esophagus earlier and the duration of bolus passing through UES was significantly longer in 10 and 20 mL compared to 3 mL (P < .05). Consequently, the onset of UES opening was significantly earlier with increased volume (P < .05). LV and TVC closure occurred later in 20 mL compared to 3 mL (P < .05). These changes in motion of pharynx and larynx appeared to promote swallow safety by preventing aspiration, suggesting that anatomical structure movements adapt in response to bolus volume. Our findings also suggest that the pharyngeal swallow behaviours may be modified by afferents in the oral cavity. The three-dimensional visualization and quantitative measurements provided by 320-ADCT provide essential benchmarks for understanding swallowing, both normal and abnormal.
Assuntos
Deglutição/fisiologia , Esfíncter Esofágico Superior/fisiologia , Osso Hioide/fisiologia , Imageamento Tridimensional , Laringe/fisiologia , Tomografia Computadorizada Multidetectores , Adulto , Fenômenos Biomecânicos , Esfíncter Esofágico Superior/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Humanos , Osso Hioide/diagnóstico por imagem , Laringe/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , ViscosidadeRESUMO
Improved diagnostic methods are needed for bronchiolitis obliterans syndrome (BOS), a serious complication after allogeneic hematopoietic cell transplantation (HCT) and lung transplantation. For protein candidate discovery, we compared plasma pools from HCT transplantation recipients with BOS at onset (n = 12), pulmonary infection (n = 16), chronic graft-versus-host disease without pulmonary involvement (n = 15) and no chronic complications after HCT (n = 15). Pools were labeled with different tags (isobaric tags for relative and absolute quantification), and two software tools identified differentially expressed proteins (≥1.5-fold change). Candidate proteins were further selected using a six-step computational biology approach. The diagnostic value of the lead candidate, matrix metalloproteinase 3 (MMP3), was evaluated by enzyme-linked immunosorbent assay in plasma of a verification cohort (n = 112) with and without BOS following HCT (n = 76) or lung transplantation (n = 36). MMP3 plasma concentrations differed significantly between patients with and without BOS (area under the receiver operating characteristic curve 0.77). Consequently, MMP3 represents a potential noninvasive blood test for diagnosis of BOS.
Assuntos
Biomarcadores/sangue , Bronquiolite Obliterante/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Pulmão/efeitos adversos , Metaloproteinase 3 da Matriz/sangue , Proteoma/análise , Adulto , Idoso , Bronquiolite Obliterante/sangue , Bronquiolite Obliterante/etiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteômica/métodos , Transplante Homólogo , Adulto JovemRESUMO
Although oropharyngeal and laryngeal structures are essential for swallowing, the three-dimensional (3D) anatomy is not well understood, due in part to limitations of available measuring techniques. This study uses 3D images acquired by 320-row area detector computed tomography ('320-ADCT'), to measure the pharynx and larynx and to investigate the effects of age, gender and height. Fifty-four healthy volunteers (30 male, 24 female, 23-77 years) underwent one single-phase volume scan (0.35 s) with 320-ADCT during resting tidal breathing. Six measurements of the pharynx and two of larynx were performed. Bivariate statistical methods were used to analyse the effects of gender, age and height on these measurements. Length and volume were significantly larger for men than for women for every measurement (P < 0.05) and increased with height (P < 0.05). Multiple regression analysis was performed to understand the interactions of gender, height and age. Gender, height and age each had significant effects on certain values. The volume of the larynx and hypopharynx was significantly affected by height and age. The length of pharynx was associated with gender and age. Length of the vocal folds and distance from the valleculae to the vocal folds were significantly affected by gender (P < 0.05). These results suggest that age, gender and height have independent and interacting effects on the morphology of the pharynx and larynx. Three-dimensional imaging and morphometrics using 320-ADCT are powerful tools for efficiently and reliably observing and measuring the pharynx and larynx.
Assuntos
Envelhecimento , Estatura , Deglutição/fisiologia , Laringe/anatomia & histologia , Tomografia Computadorizada Multidetectores , Faringe/anatomia & histologia , Caracteres Sexuais , Adulto , Idoso , Epiglote/anatomia & histologia , Feminino , Glote/anatomia & histologia , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Laringe/diagnóstico por imagem , Laringe/fisiologia , Masculino , Pessoa de Meia-Idade , Faringe/diagnóstico por imagem , Faringe/fisiologia , Valores de ReferênciaRESUMO
Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Estado Civil , Qualidade de VidaRESUMO
The combination of cyclophosphamide (CY) and total body irradiation (TBI) has been used as a standard conditioning regimen for allogeneic transplantation. Several studies showed an advantage of adding high-dose cytarabine (HDCA) to this regimen. To clarify the significance of additional HDCA, we conducted a retrospective multicenter study and compared the clinical results of these two regimens. From June 1985 to March 2003, 219 patients with hematological malignancies underwent allogeneic transplantation after conditioning with CY+TBI 12Gy (n=73) or CA+CY+TBI 12Gy (n=146). Engraftment, overall survival, transplant-related mortality (TRM), relapse rate and incidence of graft-versus-host disease (GVHD) were compared according to risks and donors. Addition of HDCA had no impact on the relapse rate in all subgroups, and it was associated with lower TRM among standard-risk patients after related transplantation, and with higher TRM and worse survival among standard-risk patients after unrelated transplantation. The incidence of acute GVHD was not significantly different between the two regimens, and HDCA resulted in a higher incidence of chronic GVHD among standard-risk patients after related transplantation. In summary, addition of HDCA is not beneficial for high-risk patients, and is not recommended for standard-risk patients receiving unrelated transplantation.
Assuntos
Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Doença Enxerto-Hospedeiro/mortalidade , Imunossupressores/administração & dosagem , Agonistas Mieloablativos/administração & dosagem , Transplante de Células-Tronco/mortalidade , Condicionamento Pré-Transplante , Adolescente , Adulto , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Doadores de Tecidos , Transplante Homólogo , Irradiação Corporal TotalRESUMO
In order to examine GvHD prophylaxis in umbilical cord blood transplantation (UCBT) in more detail, we compared transplant outcomes after UCBT for acute leukemia among GvHD prophylaxes using registry data. We selected patients transplanted with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 1516 first myeloablative UCBT between 2000 and 2012 (Cyclosporine A (CyA) plus MTX, 824, Tacrolimus (Tac) plus MTX, 554, Tac plus MMF, 138) were included. With adjusted analyses, Tac plus MMF showed a significantly higher risk for grade II-IV and III-IV acute GvHD than CyA or Tac plus MTX. Although NRM was similar, Tac plus MMF showed a significantly lower risk of relapse than CyA or Tac plus MTX. A significant difference was observed in the risk of overall mortality (OM) between the MTX-containing group and MMF-containing group. In patients with standard-risk disease, there was no significant difference in the risk of OM in any GvHD prophylaxis. However, in patients with advanced-risk disease, Tac plus MMF showed a significantly lower risk of OM. Therefore, MTX-containing prophylaxis is preferred in UCBT for standard-risk disease, whereas MMF-containing prophylaxis is preferred for advanced-risk disease. A prospective study to identify optimal GvHD prophylaxis for UCBT is warranted.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Metotrexato/administração & dosagem , Ácido Micofenólico/administração & dosagem , Adolescente , Adulto , Ciclosporina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Japão , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sistema de Registros , Taxa de Sobrevida , Tacrolimo/administração & dosagemRESUMO
In order to clarify the association between hyperglycemia during the early period after allogeneic stem cell transplantation (allo-SCT) and adverse outcomes, we retrospectively analyzed 563 consecutive patients who underwent allo-SCT at our institute between 2008 and 2015. Patients were categorized into three groups according to mean fasting blood glucose levels on days 0-7 (normoglycemia group<110 mg/dL, n=347; mild hyperglycemia group 110-149 mg/dL, n=192 and moderate/severe hyperglycemia group≥150 mg/dL, n=24). The median follow-up was 2.7 years. Patients in the moderate/severe hyperglycemia group had significantly worse characteristics. The cumulative incidences of 2-year non-relapse mortality (NRM) and the probabilities of 2-year overall survival (OS) in the normoglycemia, mild hyperglycemia and moderate/severe hyperglycemia groups were 7.5%, 19% and 29%, respectively (P<0.01), and 69%, 53% and 33%, respectively (P<0.01). In multivariate analyses, hyperglycemia was an independent predictor of high NRM (vs normoglycemia; mild hyperglycemia, hazard ratio (HR) 2.56, 95% confidence interval (CI) 1.56-4.18; moderate/severe hyperglycemia, HR 4.46, 95% CI 1.92-10.3) and poor OS (vs normoglycemia; mild hyperglycemia, HR 1.54, 95% CI 1.14-2.07; moderate/severe hyperglycemia, HR 1.61, 95% CI 0.89-2.91). In conclusion, hyperglycemia on days 0-7 after allo-SCT was associated with inferior outcomes.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hiperglicemia/diagnóstico , Adulto , Glicemia/análise , Humanos , Hiperglicemia/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
To investigate better GVHD prophylaxis in reduced intensity conditioning umbilical cord blood transplantation (RIC-UCBT), we compared transplant outcomes after UCBT among GvHD prophylaxes using the registry data. We selected patients transplanted for AML or ALL with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 748 first RIC-UCBT between 2000 and 2012 (MTX+ group, 446, MMF+ group, 302) were included. The cumulative incidence of neutrophil and platelet counts higher than 50 000/µL was significantly better in the MMF+ group (relative risk (RR), 1.55; P<0.001: RR, 1.34; P=0.003, respectively). In multivariate analyses, the risk of grade II-IV and III-IV acute GvHD was significantly higher in the MMF+ group than in the MTX+ group (RR, 1.75; P<0.001: RR, 1.97; P=0.004, respectively). In disease-specific analyses of AML, the risk of relapse of high-risk disease was significantly lower in the MMF+ group (RR, 0.69; P=0.009), whereas no significant difference was observed in the risk of relapse-free and overall survival in high-risk disease. In patients with standard-risk disease, no significant differences were noted in the risk of relapse or survival between the MTX+ and MMF+ groups. Collectively, these results suggest that MMF-containing prophylaxis may be preferable in RIC-UCBT, particularly for high-risk disease.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia/mortalidade , Leucemia/terapia , Doença Aguda , Adolescente , Soro Antilinfocitário/administração & dosagem , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Sistema de Registros , Taxa de Sobrevida , Condicionamento Pré-TransplanteRESUMO
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.
Assuntos
Doenças Cardiovasculares , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndrome Metabólica , Aloenxertos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Síndrome Metabólica/etiologia , Síndrome Metabólica/prevenção & controle , Guias de Prática Clínica como AssuntoRESUMO
The 2005 NIH chronic GVHD (cGVHD) organ severity is based on the assessment of current status regardless of whether abnormalities are due to GVHD. The score assignment does not require knowledge of past manifestations, attribution or whether cGVHD is still active. The aim of this study is to describe confounding factors affecting organ scores in patients with cGVHD. The study included 189 consecutive cGVHD patients evaluated at our center in 2013. Providers completed the NIH 0-3 organ-specific scoring evaluation with two questions added for each organ to identify abnormalities that were (i) not attributed to cGVHD or (ii) attributed to cGVHD plus other causes. Abnormalities attributed to causes other than GVHD were recorded. Eighty (14%) abnormalities were not attributed to cGVHD in at least one organ, and 41 (7%) abnormalities were attributed to cGVHD plus other causes in at least one organ. A total of 436 (78%) abnormalities were attributed only to cGVHD. Abnormalities not attributed to cGVHD were observed most frequently in the lung, gastrointestinal tract and skin. Most common abnormalities included pre-transplant condition, sequelae from GVHD, deconditioning, infections and medications. Our results support the 2014 NIH consensus recommendation to consider attribution when scoring organ abnormalities.
Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Criança , Doença Crônica , Fatores de Confusão Epidemiológicos , Feminino , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , National Institutes of Health (U.S.) , Dermatopatias/etiologia , Estados Unidos , Adulto JovemRESUMO
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has curative potential against hematological malignancies. However, there are concerns about the associated risk of non-relapse mortality (NRM). We performed a retrospective single-center study to assess changes in outcomes after allo-HSCT and causes of NRM over three 5-year periods. The rates of 2-year NRM and overall survival (OS) were 16% and 59%, respectively. We found a significant decrease in NRM (P<0.001), with 2-year NRM of 26, 14 and 9%, and a significant increase in OS (P=0.005), with 2-year OS of 52%, 58% and 65%, over the three periods (1998-2002, 2003-2007 and 2008-2012), respectively. Of note, a steady improvement was observed in NRM, period by period, among patients aged 50 years or older, patients who underwent HSCT from an unrelated bone marrow donor and patients who underwent HSCT with a reduced-intensity conditioning regimen. Our data showed that the improved NRM can mainly be attributed to a decreased mortality related to infection after starting systemic steroid as GVHD treatment, and a decreased mortality related to organ failure.
Assuntos
Bases de Dados Factuais , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoRESUMO
The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Neoplasias Meníngeas , Segunda Neoplasia Primária , Sarcoma Mieloide , Neoplasias Cutâneas , Adolescente , Adulto , Idoso , Aloenxertos , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/terapia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/terapia , Sarcoma Mieloide/mortalidade , Sarcoma Mieloide/terapia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapiaRESUMO
Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Programas de Rastreamento , Segunda Neoplasia Primária/diagnóstico , Feminino , Humanos , Masculino , Segunda Neoplasia Primária/epidemiologia , Especificidade de Órgãos , Fatores de RiscoRESUMO
New derivatives of 4-homoisotwistane (tricyclo[5.3.1.0(3,8)]undecane) (3), the olefin (8), bromide (4), alcohols (7,9,11, and 14), ketone (10), acid (12), esters (13, 18a, and 18b), amides (5, 16, and 19a-d), nitrile (20), and amines and their hydrochlorides (6, 17, and 21), were prepared, and antiviral activities of these compounds were determined in vitro on a monolayer culture of chick embryo fibroblasts against Newcastle disease virus. 4-Homoisotwist-3-ylamine hydrochloride (6) and 4-homoisotwist-3-ylmethylamine hydrochloride (21) were found 30-50 times more potent than amantadine hydrochloride in this assay. Methods of preparing the test compounds included those functionalization reactions of 3 which revealed many interesting features of the reactivity of the recently discovered polycyclic hydrocarbon 3.
Assuntos
Antivirais/síntese química , Hidrocarbonetos Aromáticos com Pontes/síntese química , Compostos Policíclicos/síntese química , Animais , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Células Cultivadas , Embrião de Galinha , Fibroblastos/metabolismo , Conformação Molecular , Vírus da Doença de Newcastle/efeitos dos fármacos , Compostos Policíclicos/farmacologia , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacosRESUMO
Convenient methods for the synthesis of 1-substituted 3-adamantyl chlorides and bromides (2), 1-adamantylphenols and -cresols (3), and 1-adamantylacetic (6) as well as 1,3-adamantanediacetic (11) acids are described. Several novel derivatives were synthesized from these key intermediates: adamantylcyclohexanols (4) and -cyclohexanones (5) from adamantylphenols (3), and esters (7,12, and 22), amides (13 and 18), thioamides (9 and 16), amidine (10), nitrile (15), and amines (14 and 17) from 1-adamantanecarboxylic (19) and -acetic (6) acids and 1,3-adamantanediacetic acid (11). Some adamantylpyrimidines (24) and -purines (25 and 26) were also prepared. Antiviral activities of the compounds obtained in this work and a series of new 1-adamantyl alkyl ketones synthesized before, together with those of some known adamantane derivatives, were tested in vitro on monolayer culture of chick ambryo fibroblasts against Newcastle disease virus.
Assuntos
Adamantano/síntese química , Antivirais/síntese química , Hidrocarbonetos Aromáticos com Pontes/síntese química , Adamantano/análogos & derivados , Adamantano/farmacologia , Animais , Células Cultivadas , Embrião de Galinha , Hemaglutinação por Vírus/efeitos dos fármacos , Vírus da Doença de Newcastle/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
Secondary (6) and tertiary (8) phosphates of exo-5,6-trimethylenenorborn-exo-2-yl alcohol (exo-tricyclo-[5.2.1.0(2,6)]dec-exo-8-yl alcohol, 3) and a secondary ester (9) of a mixture of exo-tricyclo[5.2.1.0(2,6)]dec-3-en-8- and -9-yl alcohol (2) were prepared. The most convenient route to 6 was direct esterification of phosphoric acid with 3. 9 was obtainable by the addition of phosphoric acid to endo-dicyclopentadiene (1). These phosphates were tested in vitro for antiviral activity against Newcastle disease virus using a monolayer culture of chick embryo fibroblasts. 6 was found ca. twice more potent than, while 8 was as active as, amantadine hydrochloride under the present test conditions.
Assuntos
Antivirais/síntese química , Norbornanos/síntese química , Animais , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Hemaglutinação por Vírus/efeitos dos fármacos , Vírus da Doença de Newcastle/efeitos dos fármacos , Norbornanos/farmacologia , Organofosfatos/síntese química , Organofosfatos/farmacologiaRESUMO
Functionalization reactions via cationic intermediates of tricyclo[4.3.1.1 2,5]undecane (2) were investigated to prepare derivatives with potential antiviral activities. Bromination of 2 took place regiospecifically at C-1, and the resulted bromide 5 was converted into the hydroxide 9, the carboxylic acid 12, and the amine 22, from which were synthesized a variety of secondary derivatives, including homologous esters 10 and 20, amides 14 and 19, carbamates 24, and ureas 17 and 25. The hydroxide 9, the acid 12, and the acetamide 21 were also obtainable directly from tricyclo[5.2.1.0 2,6]dec-endo-2-ylcarbinol (1), the precursor for the synthesis of the hydrocarbon 2. Success in these functionalization-rearrangements was attributed to the inability of the intermediate 2-1-yl cation (2+) for further skeletal isomerizations. Among the 1-substituted derivatives of 2 prepared, the amine hydrochlorides (16 and 23), a few esters (20b and 20d), and some N-alkylamides (19c, 19d, and 19e) exhibited marked antiviral activities as compared to amantadine hydrochloride, when tested in vitro on a monolayer culture of chick embryo fibroblasts against Newcastle disease virus.
Assuntos
Antivirais/síntese química , Compostos Policíclicos/síntese química , Animais , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Química , Embrião de Galinha , Vírus da Doença de Newcastle/efeitos dos fármacos , Compostos Policíclicos/farmacologiaRESUMO
UNLABELLED: Septal hypoperfusion is often observed in patients with complete left bundle branch block (LBBB) in myocardial perfusion imaging. Abnormal wall motion in the septal region may potentially cause artifactual perfusion abnormalities. To assess the effect of abnormal wall thickening on myocardial perfusion images, ECG-gated sestamibi SPECT was performed on 12 patients with LBBB and 10 normal subjects used as controls. METHODS: After administration of 740 MBq 99mTc-sestamibi injection at rest, ECG-gated SPECT was obtained 60 min later with division of the cardiac cycle into eight frames. RESULTS: Septal hypoperfusion was noted in 10 patients on nongated images and 11 patients on end-systolic (ES) images, whereas only two patients showed abnormalities on end-diastolic (ED) images. The septal to lateral wall count ratio in the LBBB group was lower (0.72 +/- 0.09) than in the control group (0.84 +/- 0.09) (p < 0.01) at nongated images, while it was similar at ED images (0.84 +/- 0.11 versus 0.86 +/- 0.12; ns). In addition, the count increase from ED to ES during a cardiac cycle in the septal region was smaller compared with the lateral region in the LBBB patients (25% +/- 19% in the septal region, versus 48% +/- 14% in the lateral region; p < 0.01), indicating less wall thickening in the septal region. CONCLUSION: Smaller count increase due to reduced wall thickening in the septal region may mimic hypoperfusion in patients with LBBB. This artifact can be eliminated with ECG-gated 99mTc-sestamibi SPECT, particularly with ED images.