RESUMO
OBJECTIVES: Living donor kidney transplant relieves the disease burden of patients with end-stage renal disease but may shorten donor life expectancy; however, their quality of life (QOL) is preserved. Nevertheless, the magnitude of the net gain of this procedure is unknown. We evaluated the QOL of both donors and recipients concurrently and calculated the net utility gain. METHODS: We recruited 210 subjects who visited the kidney transplantation clinic of a university hospital. Subjects were asked to complete the 5-level EQ-5D-based questionnaire, and patient characteristics were extracted from their medical records. We performed multivariate tobit models analysis to evaluate the QOL change caused by transplant surgery and subsequently ran computational simulations to determine the net utility gains of donors and recipients. We also performed sensitivity analyses. RESULTS: After excluding 16 answers with missing data, we analyzed 203 answers in total. After the transplant surgery, recipients gained 0.07 in utility value while donors lost 0.04. In the net utility analysis, we found that the quality-adjusted life years gained ranged from 7.2 to 7.8 in the most favorable case observed in the combination of middle-aged recipients and elderly donors. Assuming no utility discount, the most favorable combination was that with older donors and younger recipients. CONCLUSIONS: These findings indicated that the QOL improvement in recipients was larger than the loss among donors. When calculating the net utilities, a combination of middle-aged recipients and elderly donors yielded the largest net utility, but this was likely derived from assumption in the discount of QOL.
Assuntos
Transplante de Rim/métodos , Transplante de Rim/psicologia , Doadores Vivos/psicologia , Qualidade de Vida , Adulto , Idoso , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Obtenção de Tecidos e ÓrgãosRESUMO
PURPOSE: A newly introduced radiochromic film, the GAFCHROMIC EBT3, has been expected as much useful device for the IMRT dosimetry. The purpose of this study was to investigate the sensitivity and the uniformity of the films between an Epson ES-10000G flatbed scanner and a Vidar DosimetryPRO Advantage (Red) scanner. METHODS: Doses ranging from 1 cGy to 1600 cGy with 15-MV photon beam was irradiated to the film in a solid water phantom, respectively. All of the films were then digitized after irradiation using both two scanners. Sensitivities, local fluctuations of the film with two scanners were evaluated. Local fluctuations were defined as the relative (percent) standard deviation of the film response in ROIs (3 cmx3 cm). RESULTS: As to the Vidar scanner, the sensitivity of the film was higher for low dose range (below <400 cGy). While, as to the Epson scanner, the sensitivity using the red color channel was higher than others for low dose range. At high dose range (above >400 cGy), the green color channel had higher sensitivity than others. The Vidar scanner exhibited the lower local fluctuations than the Epson scanner for all dose ranges. For the Epson scanner, the red color channel had the lower local fluctuations than the green and blue color channel for all dose ranges. CONCLUSIONS: This study shows the characteristics of the new EBT3 films, in conjunction with the Epson ES-10000G flatbed scanner and the Vidar DosimetryPRO Advantage (Red) scanner.
RESUMO
PURPOSE: We have recently developed a dynamic tumor tracking irradiation system using Vero4DRT (MHI-Tm2 000). It is needed to create a 4D correlation model between a fiducial marker implanted near a tumor and an external surrogate as a function of time by continuously acquiring both fluoroscopy images and external surrogate signals. The purpose of this study was to propose a new dosimetry method using Gafchromic XR-SP2 films to measure surface dose by fluoroscopy imaging. METHODS: First, half-value layers (HVLs) were measured using aluminum (Al) thicknesses (15 mm) at 40125 kVp. Subsequently, several films were irradiated using various milliampere second values on a solid water phantom. The surface air kerma were also measured using the chamber to calculate the surface doses under the same condition. Then, the calibration curve of dose vs. pixel values was calculated. Finally, surface dose by fluoroscopy imaging was measured using several pieces of film taped on the chest phantom. Orthogonal X-ray fluoroscopy imaging was simultaneously performed until completion of data acquisition for creating a 4D correlation model. Those films were scanned after irradiation using a flat-bed scanner and converted to dose by calibration curve. RESULTS: The HVLs for tube voltage within 40125 kVp ranged from 2.35 to 5.98 mm Al. The calibration curve between surface dose and pixel values was reasonably smooth. The differences between the measured and the calibrated doses were less than 3%. The hot spots with the maximum dose of 37.12 mGy were observed around the area overlapped by both fluoroscopic fields. CONCLUSIONS: We have proposed a new dosimetry method using Gafchromic XR-SP2 films to measure surface dose by fluoroscopy imaging. This phantom study has demonstrated that it may be feasible to assess surface dose to patients during dynamic tumor tracking irradiation in clinic with ease after further investigation. This research was supported by the Japan Society for the Promotion of Science (JSPS) through its Funding Program for World-Leading Innovation R&D on Science and Technology (FIRST Program). Research sponsored in part by Mitsubishi Heavy Industries, Ltd.
RESUMO
PURPOSE: To perform the quality assurance for the dynamic tumor-tracking (DTT) irradiation with Vero4DRT (MHI-Tm2 000). METHODS: Vero4DRT swings its gimbaled 6-MV C-band x-ray head along the pan and tilt direction to track a moving tumor. Surrogate signal-based DTT system implemented in Vero4DRT was used. Before DTT irradiation, the correlation model (4D-model) between motion of the IR markers on the abdominal wall and the tumor position was created with synchronously monitoring by the IR camera and orthogonal kV x-ray imaging subsystem. During beam delivery, the 4D-model predicted the future tumor position from the displacement of the IR markers in real-time, and then contentiously transferred the corresponding tracking orientation to the gimbaled x-ray head.Water-equivalent phantoms were set on a 1D motor-driven base with IR markers. A film placed at a depth of 10 cm in the phantom was irradiated under the following conditions: stationary state, and tracking and non- tracking state for sinusoidal patterns. In addition, the geometric accuracy was evaluated using a 3D moving phantom and Polaris Spectra for the previously-acquired patient's respiratory pattern. RESULTS: Compared to the stationary conditions, reductions in lateral distance between 95% doses of the dose profile were 1.2 mm for tracking and 29.6 mm for non-tracking state for (amplitude [A], period [T]) = (20 mm, 2 s); and 0.2 mm and 29.4 mm for (A, T) = (20 mm, 4 s); and 0.0 mm and 11.2 mm for (A, T) = (10 mm, 2 s), respectively. In the geometric accuracy testing, 95th percentile of the tracking error was 0.5 mm in left-right, 1.0 mm in superior-inferior, and 0.5 mm in anterior-posterior direction. CONCLUSIONS: We demonstrated that Vero4DRT substantially reduced the blurring effects on dose distribution with high tracking accuracy, and confirmed the safety of the DTT irradiation for a clinical application. This research was supported by the Japan Society for the Promotion of Science (JSPS) through its Funding Program for World-Leading Innovation R&D on Science and Technology (FIRST Program), and sponsored in part by Mitsubishi Heavy Industries, Ltd.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Doenças Ovarianas/prevenção & controle , Ovário , Condicionamento Pré-Transplante , Adolescente , Adulto , Feminino , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/fisiopatologia , Humanos , Doenças Ovarianas/fisiopatologia , Transplante HomólogoRESUMO
Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated postoperative pulmonary alterations and their impact on blood oxygenation. Eighteen non-hypoxemic patients (15 men and 3 women) with normal cardiac function scheduled for CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at admission to the intensive care unit, and 12, 24, and 48 h after surgery. Pre- and postoperative volumetric thoracic CT scans were acquired under apnea conditions after a spontaneous expiration. Data were analyzed by the paired Student t-test and one-way repeated measures analysis of variance. Mean age was 63 ± 9 years. The PaO2/FiO2 ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially improving 12 h after surgery. Compared to preoperative CT, there was a 31 percent postoperative reduction in pulmonary gas volume (P < 0.001) while tissue volume increased by 19 percent (P < 0.001). Non-aerated lung increased by 253 ± 97 g (P < 0.001), from 3 to 27 percent, after surgery and poorly aerated lung by 72 ± 68 g (P < 0.001), from 24 to 27 percent, while normally aerated lung was reduced by 147 ± 119 g (P < 0.001), from 72 to 46 percent. No correlations (Pearson) were observed between PaO2/FiO2 ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. The data show that lung structure is profoundly modified after CABG with CPB. Taken together, multiple changes occurring in the lungs contribute to postoperative hypoxemia rather than atelectasis alone.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apneia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Pulmão , Análise de Variância , Apneia/etiologia , Água Corporal , Atelectasia Pulmonar/complicações , Tomografia Computadorizada por Raios XRESUMO
Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated postoperative pulmonary alterations and their impact on blood oxygenation. Eighteen non-hypoxemic patients (15 men and 3 women) with normal cardiac function scheduled for CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at admission to the intensive care unit, and 12, 24, and 48 h after surgery. Pre- and postoperative volumetric thoracic CT scans were acquired under apnea conditions after a spontaneous expiration. Data were analyzed by the paired Student t-test and one-way repeated measures analysis of variance. Mean age was 63 ± 9 years. The PaO2/FiO2 ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially improving 12 h after surgery. Compared to preoperative CT, there was a 31% postoperative reduction in pulmonary gas volume (P < 0.001) while tissue volume increased by 19% (P < 0.001). Non-aerated lung increased by 253 ± 97 g (P < 0.001), from 3 to 27%, after surgery and poorly aerated lung by 72 ± 68 g (P < 0.001), from 24 to 27%, while normally aerated lung was reduced by 147 ± 119 g (P < 0.001), from 72 to 46%. No correlations (Pearson) were observed between PaO2/FiO2 ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. The data show that lung structure is profoundly modified after CABG with CPB. Taken together, multiple changes occurring in the lungs contribute to postoperative hypoxemia rather than atelectasis alone.
Assuntos
Apneia/diagnóstico por imagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Pulmão/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Apneia/etiologia , Água Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atelectasia Pulmonar/complicações , Tomografia Computadorizada por Raios XRESUMO
Since we reported the first successful case of allogeneic hematopoietic SCT (allo-HSCT), we have performed allo-HSCT for 29 patients with chronic active EBV infection (CAEBV), using either myeloablative conditioning (MAC) allo-HSCT (MAST) or reduced-intensity conditioning (RIC) allo-HSCT (RIST). In this retrospective analysis we compared the outcomes after MAST and RIST to identify the optimal conditioning for patients with CAEBV. Of 29 patients, 11 underwent allo-HSCT with MAC, consisting of TBI (12 Gy), etoposide (900 mg/m²) and CY (120 mg/kg) or melphalan (210 mg/m²), and the remaining 18 patients received allo-HSCT after RIC, consisting of fludarabine (â¼ 180 mg/m²) and melphalan (140 mg/m²) or CY (120 mg/kg), with/without antithymocyte globulin and low-dose irradiation. Donor sources were 8 related BM, 2 related peripheral blood, 5 CD34 selected cells from HLA-haploidentical donors, 8 unrelated BM and 8 unrelated cord blood. The 3-year-EFS rate was 54.5 ± 15.0% for MAST group and 85.0 ± 8.0% for RIST group, and the 3-year OS rate was 54.5 ± 15.0% for MAST group and 95.0 ± 4.9% for RIST group (P = 0.016). Allo-HSCT after RIC seems to be a promising approach for the treatment of CAEBV.
Assuntos
Infecções por Vírus Epstein-Barr/terapia , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Antígenos CD/metabolismo , Antivirais/uso terapêutico , Criança , Pré-Escolar , Doença Crônica , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Herpesvirus Humano 4/isolamento & purificação , Humanos , Lactente , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Masculino , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Carga Viral , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: The lipid phosphatase known as SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) plays an important role in the regulation of the intracellular insulin signalling pathway. Recent studies have suggested that inhibition of SHIP2 could produce significant benefits in treatment of type 2 diabetes. However, there were no small molecule SHIP2 inhibitors and we, therefore, aimed to identify this type of compound. EXPERIMENTAL APPROACH: The phosphatase assay with malachite green was used for high-throughput screening. The pharmacological profiles of suitable compounds were further characterized in phosphatase assays, cellular assays and oral administration in normal and diabetic (db/db) mice. KEY RESULTS: During high-throughput screening, AS1949490 was identified as a potent SHIP2 inhibitor (IC(50)= 0.62 microM for SHIP2). This compound was also selective for SHIP2 relative to other intracellular phosphatases. In L6 myotubes, AS1949490 increased the phosphorylation of Akt, glucose consumption and glucose uptake. In FAO hepatocytes, AS1949490 suppressed gluconeogenesis. Acute administration of AS1949490 inhibited the expression of gluconeogenic genes in the livers of normal mice. Chronic treatment of diabetic db/db mice with AS1949490 significantly lowered the plasma glucose level and improved glucose intolerance. These in vivo effects were based in part on the activation of intracellular insulin signalling pathways in the liver. CONCLUSIONS AND IMPLICATIONS: This is the first report of a small molecule inhibitor of SHIP2. This compound will help to elucidate the physiological functions of SHIP2 and its involvement in various diseases, such as type 2 diabetes.
Assuntos
Monoéster Fosfórico Hidrolases/metabolismo , Tiofenos/farmacologia , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Intolerância à Glucose/sangue , Intolerância à Glucose/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Inositol Polifosfato 5-Fosfatases , Insulina/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/genética , Fosforilação , Período Pós-Prandial , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Tiofenos/uso terapêutico , Domínios de Homologia de srcAssuntos
Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA/imunologia , Leucemia/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Mães , Núcleo Familiar , Prognóstico , Taxa de Sobrevida , Doadores de Tecidos , Resultado do Tratamento , Adulto JovemRESUMO
Eight children underwent reduced-intensity stem cell transplantation (RIST) from an HLA-matched sibling. They received a fludarabine-melphalan based preparative regimen. Stem cell source was bone marrow, and GVHD prophylaxis consisted of cyclosporine A alone. Acute GVHD grade II-IV and grade III-IV were observed in four (50%) and three (37.5%), respectively, out of these eight patients. This incidence was significantly higher than that after conventional bone marrow transplantation, without severe tissue damage, in the same setting of stem cell source and GVHD prophylaxis. Although the number of patients is small, our results suggest that incidence of acute GVHD after RIST for children is significant. It should be remembered that RIST for children does not seem to be an easy transplant procedure from the viewpoint of acute GVHD, although RIST is less toxic.
Assuntos
Transplante de Medula Óssea/métodos , Doença Enxerto-Hospedeiro/epidemiologia , Teste de Histocompatibilidade , Leucemia/terapia , Linfoma/terapia , Neoplasias/terapia , Transplante de Células-Tronco/métodos , Adolescente , Contagem de Células , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Incidência , Lactente , Japão , Masculino , Estudos RetrospectivosRESUMO
1. The mechanisms involved in the fine adjustment of iris sphincter muscle tone are largely unknown. The aim of the present study was to clarify the effects of adrenomedullin on the resting tension of the bovine isolated iris sphincter muscle. 2. The motor activity of the bovine isolated iris sphincter muscle was measured isometrically. The effects of adrenomedullin on resting tension were analysed in the presence of indomethacin. The presence of adrenomedullin mRNA in the preparation was determined by reverse transcription-polymerase chain reaction. Immunolabelling for adrenomedullin was also performed. 3. Adrenomedullin significantly decreased the resting tension of the muscle. The relaxant effect of adrenomedullin was significantly inhibited by adrenomedullin (22-52), a putative antagonist for the adrenomedullin receptor, or calcitonin gene-related peptide (CGRP) (8-37), a putative antagonist for the CGRP1 receptor. The relaxant effect was almost completely blocked by a combination of adrenomedullin (22-52) and CGRP (8-37). 4. The relaxant effect of adrenomedullin was also significantly diminished by 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. 5. Reverse transcription-polymerase chain reaction analysis showed that adrenomedullin mRNA was expressed in the muscle strip. Immunopositive staining for adrenomedullin was detected in blood vessel cells and in the iris sphincter muscle cells. 6. These results suggest that adrenomedullin may be an autocrine and paracrine regulator of the resting tension of the iris sphincter muscle. Its biological effects may be due to the direct involvement of adrenomedullin receptors and also to the stimulation of CGRP1 receptors. The stimulation of these receptors by the peptide leads to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the muscle strip.
Assuntos
Peptídeos/farmacologia , Pupila/efeitos dos fármacos , Adrenomedulina , Animais , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Bovinos , Didesoxiadenosina/análogos & derivados , Didesoxiadenosina/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Técnicas In Vitro , Indometacina/farmacologia , Masculino , Contração Muscular/efeitos dos fármacos , Nitroarginina/farmacologia , Oxidiazóis/farmacologia , Fragmentos de Peptídeos/farmacologia , Quinoxalinas/farmacologia , Transdução de SinaisRESUMO
In all, 100 unrelated donor bone marrow transplantations (UD-BMT) were performed in our institute between October 1993 and January 2003. Of 93 evaluable patients, 73 patients had hematological malignancy, 13 had nonmalignancy and seven had lymphoproliferative disease. The estimated 9-year event-free survival (EFS) rate was 57.1+/-5.5% in all patients. In the following analyses of the patients with hematological malignancy, the standard group had significantly better EFS than the high-risk group (61.5+/-7.0 vs 35.6+/-9.7%, P=0.02), and the EFS rate of the tacrolimus (FK-506)+methotrexate (MTX)+/-methylprednisolone prophylactic group for graft-versus-host disease was superior to that of the FK-506 without MTX group (75.7+/-8.0 vs 55.8+/-7.6%, P=0.02). When we compared the EFS rates of the FK506+MTX+/-methylprednisolone (mPSL) group and the HLA-matched related donor BMT group in our institute, these were almost similar (75.7+/-8.1 vs 68.4+/-9.3%). Therefore, UD-BMT using FK-506+MTX+/-mPSL is a safe and useful method for children with hematological malignancy who require allogeneic BMT.
Assuntos
Transplante de Medula Óssea/métodos , Doadores de Tecidos , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/imunologia , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/etiologia , Doença Enxerto-Hospedeiro/induzido quimicamente , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/complicações , Doenças Hematológicas/mortalidade , Doenças Hematológicas/terapia , Humanos , Lactente , Japão , Masculino , Metotrexato/uso terapêutico , Metilprednisolona/uso terapêutico , Pré-Medicação , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Tacrolimo/toxicidadeRESUMO
Recent findings indicate that Epstein-Barr virus (EBV)-infected T-/natural killer (NK) cells play an important role in the pathogenesis of mosquito allergy, and most patients with mosquito allergy die early in life if not properly treated. Over the last 7 years, we have been using combination chemotherapy and allogeneic stem cell transplantation for the treatment of EBV-associated T-/NK cell lymphoproliferative disease (LPD) in which chronic active EBV infection and mosquito allergy were included. As of this writing, we have successfully treated 2 patients with mosquito allergy with chemotherapy in which EBV-infected T-/NK cells were eradicated. The findings suggest the possible role of chemotherapy in the treatment of EBV-associated T-/NK cell LPD.
Assuntos
Culicidae , Infecções por Vírus Epstein-Barr/terapia , Hipersensibilidade Imediata/terapia , Mordeduras e Picadas de Insetos/terapia , Células Matadoras Naturais , Transtornos Linfoproliferativos/terapia , Linfócitos T , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Feminino , Humanos , Hipersensibilidade Imediata/complicações , Hipersensibilidade Imediata/patologia , Mordeduras e Picadas de Insetos/complicações , Mordeduras e Picadas de Insetos/patologia , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/patologia , Masculino , Indução de Remissão/métodos , Transplante de Células-Tronco/métodos , Linfócitos T/patologia , Linfócitos T/virologia , Transplante HomólogoAssuntos
Proteínas de Ligação a DNA/genética , Leucemia Mielomonocítica Aguda/genética , Proteínas de Fusão Oncogênica/genética , Proto-Oncogenes , Fatores de Transcrição , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 12/genética , Proteínas de Ligação a DNA/metabolismo , Rearranjo Gênico , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Masculino , Proteína Quinase 8 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Dados de Sequência Molecular , Proteína de Leucina Linfoide-Mieloide , Proteínas Nucleares , Estrutura Terciária de Proteína , Translocação GenéticaRESUMO
The authors present the case of a newborn girl with extreme fenestration of the basilar artery. This anomaly was found incidentally during MR imaging study for cleft palate and nasopharyngeal teratoma. Magnetic resonance angiography showed a totally duplicated basilar artery with connections at the proximal and distal ends of the artery, suggesting an extreme fenestration. Duplicated pituitary gland was also found on MR imaging.
Assuntos
Anormalidades Múltiplas/diagnóstico , Artéria Basilar/anormalidades , Fissura Palatina/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Hipófise/anormalidades , Teratoma/diagnóstico , Fissura Palatina/complicações , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas/complicações , Teratoma/complicaçõesRESUMO
Human herpesvirus 6 (HHV-6) infection and disease are serious complications of allogeneic hematopoietic stem cell transplantation (allo-SCT). Ganciclovir (GCV) is effective against HHV-6 in vitro but the antiviral susceptibility of HHV-6 has not been well characterized in vivo. We retrospectively compared the HHV-6 reactivation rate in pediatric allo-SCT recipients with and without GCV prophylaxis. The HHV-6 reactivation rate at 3 weeks after allo-SCT in patients without prophylactic GCV administration was significantly higher than that in those receiving prophylactic GCV (11/28 vs 0/13, P < 0.01). Five of 36 patients without prophylactic GCV showed clinical manifestations including skin rash, interstitial pneumonitis, persistent thrombocytopenia, enterocolitis and thrombotic microangiopathy, respectively. HHV-6-associated symptoms were observed in one of the 13 patients receiving prophylactic GCV. This patient showed fever, diarrhea and graft rejection concomitantly with a sudden increase of HHV-6 DNA copy number. Patients who received GCV for treatment of HHV-6 infection showed an improvement in symptoms and/or decrease of HHV-6 copy number. Thus, GCV is effective for treating HHV-6 disease after allo-SCT in vivo.
Assuntos
Antivirais/uso terapêutico , Ganciclovir/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6/efeitos dos fármacos , Infecções por Roseolovirus/prevenção & controle , Criança , DNA Viral/sangue , Avaliação de Medicamentos , Feminino , Herpes Zoster/prevenção & controle , Herpesvirus Humano 6/crescimento & desenvolvimento , Herpesvirus Humano 6/isolamento & purificação , Humanos , Masculino , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Infecções por Roseolovirus/tratamento farmacológico , Infecções por Roseolovirus/epidemiologia , Infecções por Roseolovirus/mortalidade , Transplante Homólogo , Viremia/tratamento farmacológico , Ativação Viral/efeitos dos fármacosRESUMO
Cyclosporine A (CsA) may increase the incidence of thrombotic events, but whether tacrolimus (Tc) has such effects is still unclear. The serotonergic system has been linked to the thrombotic effects of CsA, but a direct effect of CsA on serotonin-induced platelet aggregation has not been demonstrated because of methodological difficulties. We measured the effects of CsA and Tc on serotonin-induced platelet aggregate formation by particle counting using light scattering. CsA and Tc both enhanced serotonin-induced formation of small platelet aggregates, however, neither CsA nor Tc affected aggregation induced by high or low concentrations of ADP, with or without addition of a serotonin receptor antagonist. Both CsA and Tc enhance platelet aggregation induced via the serotonin pathway.
Assuntos
Ciclosporina/farmacologia , Imunossupressores/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Serotonina/fisiologia , Tacrolimo/farmacologia , Difosfato de Adenosina/farmacologia , Transplante de Medula Óssea/efeitos adversos , Sinergismo Farmacológico , Humanos , Técnicas In Vitro , Luz , Espalhamento de Radiação , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Trombofilia/induzido quimicamenteRESUMO
Unrelated cord blood transplantation (CBT) has been worldwide for bone marrow reconstitution. CBT is associated with a high frequency of engraftment failure and rejection due to a small dose of graft cells. In cases of engraftment failure or rejection following unrelated CBT, retransplantation from the original donors is impossible. We report a successful transplantation with CD34+ blood cells selected from a 2-loci HLA-mismatched mother to a child with acute monocytic leukemia after engraftment failure of the primary CBT. Selected CD34+ blood cell transplantation is a useful approach for retransplantation in the setting of engraftment failure.