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1.
Med Oral Patol Oral Cir Bucal ; 24(6): e746-e751, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31655834

RESUMEN

BACKGROUND: The aim of this study was to compare the anti-inflammatory effects of dexamethasone and etoricoxib after third molar extraction. MATERIAL AND METHODS: A prospective, randomized, controlled, split-mouth study was conducted. 19 volunteers were allocated randomly to receive 90mg etoricoxib 1 hour prior to the procedure or 4mg intramuscular dexamethasone immediately after anesthesia. Baseline measurements were obtained preoperatively, and subsequent assessments were made on immediate postoperative, at 72 hours and 7 days after surgery to measure postoperative facial swelling by use of linear measurements, interincisal mouth opening width and visual analog scale score for pain. The amount of analgesics consumed was recorded. Descriptive statistics and the independent-samples t-test were used to compare the two groups at P < 0.05. RESULTS: Dexamethasone was effective in the control roasted edema for measurements of the mandibular angle - wing of the nose and mandibular angle - labial commissure 72 hours after surgery. And for the measurement mandibular angle - mentum, in the time of 72 hours and 7 days. There was no statistically significant difference in relation to pain and trismus. CONCLUSIONS: Considering significant results for some measures of the variable edema for the group that used intramuscular dexamethasone and the difference without statistical significance between groups for the other variables studied, we seem to reflect the intramuscular indication of the corticosteroid in a single dosage in relation to the use of etoricoxib as pre-emptive medication.


Asunto(s)
Tercer Molar , Diente Impactado , Antiinflamatorios , Dexametasona , Método Doble Ciego , Edema , Etoricoxib , Humanos , Dimensión del Dolor , Dolor Postoperatorio , Estudios Prospectivos , Extracción Dental , Trismo
2.
Ann Oncol ; 28(2): 386-392, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28426102

RESUMEN

Background: Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking. Patients and methods: We evaluated infection-related complications that were grade ≥3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period. Results: Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively. Among documented infection episodes, upper respiratory tract was the most common site (n = 389), followed by ear (n = 151), bloodstream (n = 147), and gastrointestinal tract (n = 145) infections. These episodes were more common during intensified therapy phases such as remission induction and reinduction, but respiratory and ear infections, presumably viral in origin, also occurred during continuation phases. The 3-year cumulative incidence of infection-related death was low (1.0±0.9%, n = 4), including 2 from Bacillus cereus bacteremia. There was no fungal infection-related mortality. Age 1-9.9 years at diagnosis was associated with febrile neutropenia (P = 0.002) during induction and febrile neutropenia and documented infection (both P < 0.001) during later continuation. White race was associated with documented infection (P = 0.034) during induction. Compared with low-risk patients, standard- and high-risk patients received more intensive therapy during early continuation and had higher incidences of febrile neutropenia (P < 0.001) and documented infections (P = 0.043). Furthermore, poor neutrophil surge after dexamethasone pulses during continuation, which can reflect the poor bone marrow reserve, was associated with infections (P < 0.001). Conclusions: The incidence of infection-related death was low. However, young age, white race, intensive chemotherapy, and lack of neutrophil surge after dexamethasone treatment were associated with infection-related complications. Close monitoring for prompt administration of antibiotics and modification of chemotherapy should be considered in these patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/mortalidad , Neutropenia Febril Inducida por Quimioterapia/terapia , Niño , Preescolar , Dexametasona/administración & dosificación , Femenino , Humanos , Lactante , Recuento de Leucocitos , Masculino , Neutrófilos/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Infecciones del Sistema Respiratorio/inducido químicamente , Infecciones del Sistema Respiratorio/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Vincristina/administración & dosificación
3.
Pediatr Blood Cancer ; 61(5): 803-9, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24376115

RESUMEN

BACKGROUND: Five Asociación de Hemato-Oncología de Centroamérica (AHOPCA) countries have used an adapted BFM-based protocol for childhood acute lymphoblastic leukemia (ALL). PROCEDURE: In the AHOPCA-ALL 2008 protocol, patients were stratified by age, white blood cell count, immunophenotype, central nervous system involvement, day 8 prednisone response, and morphologic bone marrow response to induction therapy. Patients at Standard Risk (SR) received a three-drug induction regimen, a reinduction phase, and maintenance with protracted intrathecal therapy. Those at Intermediate (IR) and High Risk (HR) received, in addition, daunorubicin during induction therapy, a consolidation phase and two or three reinduction phases respectively. RESULTS: From August 2008 through July 2012, 1,313 patients were enrolled: 353 in SR, 548 in IR, 412 in HR. During induction therapy, 3.0% of patients died, 2.7% abandoned treatment, 1.1% had resistant ALL, and 93.2% achieved morphological complete remission (CR). Deaths and abandonment in first CR occurred in 2.7% and in 7.0% of patients, respectively. The relapse rate at a median observation time of 2.1 years was 15.0%. At 3 years, the event-free survival (EFS) and overall survival (OS), with abandonment considered as an event, were 59.4% (SE 1.7) and 68.2% (SE 1.6). Three-year EFS was 68.5% (SE 3.0), 62.1% (SE 2.6), and 47.8% (SE 3.2) for SR, IR, and HR groups. Adolescents had a significantly higher relapse rate (P = 0.001). CONCLUSIONS: This experience shows that common international studies are feasible in lower-middle income countries. Toxic deaths, abandonment of treatment, and relapses remain major obstacles to the successful treatment. Alternative treatment strategies may be beneficial.


Asunto(s)
Países en Desarrollo , Recurrencia Local de Neoplasia/terapia , Neoplasias Primarias Secundarias/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Privación de Tratamiento/estadística & datos numéricos , Adolescente , América Central , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Renta , Lactante , Recién Nacido , Masculino , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/mortalidad , Pobreza , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Inducción de Remisión , Tasa de Supervivencia , Privación de Tratamiento/economía
4.
J Hum Nutr Diet ; 27(2): 162-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24387274

RESUMEN

BACKGROUND: Measures of central adiposity such as waist circumference (PC) and sagittal abdominal diameter (SAD) are better predictors of metabolic complications than measures of total body fat. Thus, this study aimed to assess the relationship of different measures of WC and SAD with cardiometabolic risk factors in elderly men. METHODS: This is a cross-sectional study that included 69 men (aged 60-92 years old) enrolled in the Family Health Program of Viçosa, Minas Gerais, Brazil. The evaluations comprised anthropometric, biochemical and haemodynamic measurements. The WC (i.e., umbilical level; the narrowest waist; immediately above the iliac crests; and the midpoint between the last rib and iliac crest) and SAD (i.e., the narrowest point between the last rib and the iliac crest; higher abdominal diameter; umbilical level; and the midpoint between the iliac crests) were measured at different anatomical sites. Statistical analysis consisted of correlation coefficients between measures of abdominal adiposity and cardiometabolic risk factors. RESULTS: The strongest correlations were between the WC measured at the narrowest waist and triglycerides (TG), fasting blood glucose (FBG) and high-density lipoprotein cholesterol (HDL-C) levels, and between the SAD measured at the midpoint between the iliac crests and TG, FBG and HDL-C. CONCLUSIONS: SAD measured at the midpoint between the iliac crests and WC measured at the narrowest waist showed the best relationships with cardiometabolic risk factors in elderly men.


Asunto(s)
Abdomen , Adiposidad , Enfermedades Cardiovasculares/etiología , Obesidad Abdominal/complicaciones , Diámetro Abdominal Sagital , Circunferencia de la Cintura , Anciano , Anciano de 80 o más Años , Antropometría , Glucemia/metabolismo , Brasil , Enfermedades Cardiovasculares/sangre , HDL-Colesterol/sangre , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/sangre , Factores de Riesgo , Triglicéridos/sangre
5.
Ann Oncol ; 24(9): 2425-9, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23788752

RESUMEN

BACKGROUND: Reliable prognostic factors have not been established for advanced-stage pediatric lymphoblastic lymphoma (LL). We analyzed treatment outcomes and potential risk factors in children and adolescents with advanced-stage LL treated over a 40-year period. PATIENTS AND METHODS: From 1962 through 2002, 146 patients (99 boys and 47 girls) with stage III (n = 111) or stage IV (n = 35) LL were treated at St Jude Children's Research Hospital. The five treatment eras were 1962-1975 (no protocol), 1975-1979 (NHL-75), 1979-1984 (Total 10 High), 1985-1992 (Pediatric Oncology Group protocol), and 1992-2002 (NHL13). Age at diagnosis was <10 years in 65 patients and ≥10 years in 81. RESULTS: Outcomes improved markedly over successive treatment eras. NHL13 produced the highest 5-year event-free survival (EFS) estimate (82.9% ± 6.1% [SE]) compared with only 20.0% ± 8.0% during the earliest era. Treatment era (P < 0.0001) and age at diagnosis (<10 years versus ≥10 years, P = 0.0153) were independent prognostic factors, whereas disease stage, lactate dehydrogenase level, and presence of a pleural effusion were not. CONCLUSIONS: Treatment era and age were the most important prognostic factors for children with advanced-stage LL. We suggest that a better assessment of early treatment response may help to identify patients with drug-resistant disease who require more intensive therapy.


Asunto(s)
Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Niño , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Factores de Riesgo , Resultado del Tratamiento
6.
Acta Haematol ; 130(1): 23-6, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23363773

RESUMEN

Acute promyelocytic leukemia (APL) is usually associated with a favorable outcome, but about 10% of patients tend to relapse. The genetic hallmark of APL is a balanced translocation involving chromosomes 15 and 17, and the PML-RARa gene fusion is found in more than 90% of these cases. Other chromosomal abnormalities are commonly found in APL, but their clinical significance has yet to be determined. Here we report a case of childhood APL that was studied by conventional cytogenetics along with molecular cytogenetic techniques. The patient showed a complex karyotype with an unusual cytogenetic rearrangement originating from two different abnormalities in a single chromosome 6. Our case is an exceptional example of a cryptic cytogenetic anomaly in APL and underscores the importance of detailed genetic characterization.


Asunto(s)
Cromosomas Humanos Par 6 , Reordenamiento Génico , Leucemia Promielocítica Aguda/genética , Translocación Genética/genética , Niño , Bandeo Cromosómico , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 17 , Humanos , Hibridación Fluorescente in Situ , Masculino
7.
Sci Rep ; 13(1): 1508, 2023 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-36707603

RESUMEN

Topological one-dimensional superconductors can sustain zero energy modes protected by different kinds of symmetries in their extremities. Observing these excitations in the form of Majorana fermions is one of the most intensive quests in condensed matter physics. We are interested in another class of one-dimensional topological systems in this work, namely topological insulators. Which present symmetry-protected end modes with robust properties and do not require the low temperatures necessary for topological superconductivity. We consider a device in the form of a single electron transistor coupled to the simplest kind of topological insulators, namely chains of atoms with hybridized sp orbitals. We study the thermoelectric properties of the device in the trivial, non-trivial topological phases and at the quantum topological transition of the chains. We show that the device's electrical conductance and the Wiedemann-Franz ratio at the topological transition have universal values at very low temperatures. The conductance and thermopower of the device with diatomic sp-chains, at their topological transition, give direct evidence of fractional charges in the system. The former has an anomalous low-temperature behavior, attaining a universal value that is a consequence of the double degeneracy of the system due to the presence of zero energy modes. On the other hand, the system can be tuned to exhibit high values of the thermoelectric figure of merit and the power factor at high temperatures.

8.
Sci Rep ; 13(1): 17965, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37863891

RESUMEN

We theoretically propose penta-silicene nanoribbons (p-SiNRs) with induced p-wave superconductivity as a platform for the emergence of spin-polarized Majorana zero-modes (MZMs). The model explicitly considers the key ingredients of well-known Majorana hybrid nanowire setups: Rashba spin-orbit coupling, magnetic field perpendicular to the nanoribbon plane, and first nearest neighbor hopping with p-wave superconducting pairing. The energy spectrum of the system, as a function of chemical potential, reveals the existence of MZMs with a well-defined spin orientation localized at the opposite ends of both the top and bottom chains of the p-SiNR, associated with well-localized and nonoverlapping wave function profiles. Well-established experimental techniques enable the fabrication of highly ordered p-SiNRs, complemented by a thin lead film on top, responsible for inducing p-wave superconductivity through proximity effect. Moreover, the emergence of MZMs with explicit opposite spin orientations for some set of model parameters opens a new avenue for exploring quantum computing operations, which accounts for both MZMs and spin properties, as well as for new MZMs probe devices based on spin-polarized electronic transport mechanisms.

9.
Cancer Genet ; 262-263: 16-22, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34974289

RESUMEN

Intrachromosomal amplification of chromosome 21 (iAMP21) occurs in ∼2% of B-cell acute lymphoblastic leukemia (ALL) and is considered to confer a poor prognosis. The relapse risk is associated with therapy intensity, suggesting that other somatic mutations may influence iAMP21-ALL prognosis. This abnormality is characterized by multiple copies of the RUNX1 gene in chromosome 21 and appears to arise through multiple breakage-fusion bridge cycles and chromothripsis. Rob(15;21) or a ring chromosome 21 have been associated with an increased risk for iAMP21-ALL, suggesting that constitutional genetic abnormalities may also drive leukemogenesis. Here we describe homozygous deletion of the SH2B3 gene, chromothripsis of chromosome 21, and a non-Robertsonian somatic t(15;21)(q25.3;q22.1) with NTRK3 gene rearrangement in an adolescent with iAMP21-B-ALL. Molecular cytogenetic studies detected iAMP21 with aCGH analysis revealing further genomic imbalances. The RT-qPCR analysis detected elevated expression levels of RUNX1 (68-fold) and reduced expression of CDK6 (0.057-fold). Studies with constitutive cells collected from mouth swabs showed that SH2B3 biallelic deletion was a somatic alteration occurring during clonal evolution. The identification of novel secondary genetic changes was valuable to discuss sporadic iAMP21 leukemogenic mechanisms. For the first time, we show a t(15;21)(q25.3;q22.1) with NTRK3 rearrangement in an adolescent with iAMP21-ALL.


Asunto(s)
Linfoma de Burkitt , Cromotripsis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Cromosomas en Anillo , Adolescente , Linfoma de Burkitt/genética , Cromosomas Humanos Par 21/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Homocigoto , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Células Precursoras de Linfocitos B , Eliminación de Secuencia , Translocación Genética
10.
Ann Oncol ; 22(2): 468-71, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20624787

RESUMEN

BACKGROUND: Children with recurrent or refractory malignant lymphoma generally have a poor prognosis. There is a need for new active drug combinations for this high-risk group of patients. PATIENTS AND METHODS: This study evaluated the activity and toxicity of the methotrexate, ifosfamide, etoposide and dexamethasone (MIED) regimen for childhood refractory/recurrent non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma (HL). From 1991 through 2006, 62 children with refractory/recurrent NHL (n = 24) or HL (n = 38) received one to six cycles of MIED. Based on MIED response, intensification with hematopoietic stem cell transplantation (HSCT) was considered. RESULTS: There were 10 complete (CR) and 5 partial responses (PR) among the 24 children with NHL [combined response rate, 63%; 95% confidence interval (CI) 38% to 73%]. There were 13 CR and 18 PR among the 37 assessable children with HL (combined response rate, 84%; 95% CI, 68% to 94%). Although 59% courses were associated with grade IV neutropenia, treatment was well tolerated and without toxic deaths. CONCLUSIONS: MIED is an effective regimen for refractory/recurrent childhood malignant lymphoma, permitting a bridge to intensification therapy with HSCT.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Dexametasona/administración & dosificación , Etopósido/administración & dosificación , Enfermedad de Hodgkin/patología , Humanos , Ifosfamida/administración & dosificación , Linfoma no Hodgkin/patología , Metotrexato/administración & dosificación , Recurrencia , Terapia Recuperativa
11.
Clin Oncol (R Coll Radiol) ; 33(4): e211-e220, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33250288

RESUMEN

AIMS: Childhood cancer survival is suboptimal in most low- and middle-income countries (LMICs). Radiotherapy plays a significant role in the standard care of many patients. To assess the current status of paediatric radiotherapy, the International Atomic Energy Agency (IAEA) undertook a global survey and a review of practice in eight leading treatment centres in middle-income countries (MICs) under Coordinated Research Project E3.30.31; 'Paediatric radiation oncology practice in low and middle income countries: a patterns-of-care study by the International Atomic Energy Agency.' MATERIALS AND METHODS: A survey of paediatric radiotherapy practices was distributed to 189 centres worldwide. Eight leading radiotherapy centres in MICs treating a significant number of children were selected and developed a database of individual patients treated in their centres comprising 46 variables related to radiotherapy technique. RESULTS: Data were received from 134 radiotherapy centres in 42 countries. The percentage of children treated with curative intent fell sequentially from high-income countries (HICs; 82%) to low-income countries (53%). Increasing deficiencies were identified in diagnostic imaging, radiation staff numbers, radiotherapy technology and supportive care. More than 92.3% of centres in HICs practice multidisciplinary tumour board decision making, whereas only 65.5% of centres in LMICs use this process. Clinical guidelines were used in most centres. Practice in the eight specialist centres in MICs approximated more closely to that in HICs, but only 52% of patients were treated according to national/international protocols whereas institution-based protocols were used in 41%. CONCLUSIONS: Quality levels in paediatric radiotherapy differ among countries but also between centres within countries. In many LMICs, resources are scarce, coordination with paediatric oncology is poor or non-existent and access to supportive care is limited. Multidisciplinary treatment planning enhances care and development may represent an area where external partners can help. Commitment to the use of protocols is evident, but current international guidelines may lack relevance; the development of resources that reflect the capacity and needs of LMICs is required. In some LMICs, there are already leading centres experienced in paediatric radiotherapy where patient care approximates to that in HICs. These centres have the potential to drive improvements in service, training, mentorship and research in their regions and ultimately to improve the care and outcomes for paediatric cancer patients.


Asunto(s)
Neoplasias , Energía Nuclear , Oncología por Radiación , Niño , Países en Desarrollo , Humanos , Agencias Internacionales , Oncología Médica , Neoplasias/radioterapia
12.
Science ; 280(5370): 1747-9, 1998 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-9624051

RESUMEN

The ligand-binding domain of nuclear receptors contains a transcriptional activation function (AF-2) that mediates hormone-dependent binding of coactivator proteins. Scanning surface mutagenesis on the human thyroid hormone receptor was performed to define the site that binds the coactivators, glucocorticoid receptor-interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1). The residues involved encircle a small surface that contains a hydrophobic cleft. Ligand activation of transcription involves formation of this surface by folding the carboxyl-terminal alpha helix against a scaffold of three other helices. These features may represent general ones for nuclear receptors.


Asunto(s)
Receptores de Hormona Tiroidea/química , Receptores de Hormona Tiroidea/metabolismo , Factores de Transcripción/metabolismo , Activación Transcripcional , Triyodotironina/metabolismo , Células HeLa , Histona Acetiltransferasas , Humanos , Ligandos , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Coactivador 1 de Receptor Nuclear , Coactivador 2 del Receptor Nuclear , Conformación Proteica , Pliegue de Proteína , Estructura Secundaria de Proteína , Receptores de Ácido Retinoico/metabolismo , Receptores de Hormona Tiroidea/genética , Proteínas Recombinantes de Fusión/metabolismo , Receptores X Retinoide , Triyodotironina/farmacología
13.
Braz J Biol ; 79(3): 377-382, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30484477

RESUMEN

Brazil is a leading palm oil producer, but the defoliating caterpillars Opsiphanes invirae Hübner Brassolis sophorae L. (Lepidoptera: Nymphalidae) can reduce the productivity of this crop. The aim of this study was to evaluate the development and reproduction of the parasitoid Trichospilus diatraeae Cherian & Margabandhu (Hymenoptera: Eulophidae) in pupae of these oil palm defoliators. Ten O. invirae or B. sophorae pupae with up to two days old were exposed each to 30 T. diatraeae females for 48 hours. Parasitism and emergence of the progeny of T. diatraeae were similar in pupae of both Lepidoptera defoliators. The life cycle of this parasitoid was shorter in O. invirae (21.50 ± 0.42 days) pupae than with those of B. sophorae (27.60 ± 1.80 days). The number of the progeny (669.00 ± 89.62) and dead immature (217.13 ± 58.18) of T. diatraeae were higher in B. sophorae pupae than in those of O. invirae with 447.83 ± 51.52 and 13.50 ± 5.23, respectively. The sex ratio and female and male longevity of T. diatraeae emerged from these hosts were similar. The reproductive traits, especially the number of individuals (offspring) of T. diatraeae were better with B. sophorae pupae than with those of O. invirae.


Asunto(s)
Mariposas Diurnas/parasitología , Herbivoria , Interacciones Huésped-Parásitos , Avispas/fisiología , Animales , Arecaceae/crecimiento & desarrollo , Brasil , Mariposas Diurnas/crecimiento & desarrollo , Femenino , Larva/crecimiento & desarrollo , Larva/parasitología , Larva/fisiología , Masculino , Hojas de la Planta/crecimiento & desarrollo , Reproducción , Avispas/crecimiento & desarrollo
14.
J Med Genet ; 43(1): 91-6, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16033918

RESUMEN

BACKGROUND: An inherited germline P53 mutation has been identified in cases of childhood adrenocortical carcinoma (ACT), a neoplasm with a high incidence in southern Brazil. The penetrance of ACT in carriers of the point mutation, which encodes an arginine-to-histidine substitution at codon 337 of TP53 (R337H), has not been determined. OBJECTIVE: To investigate the penetrance of childhood ACT in carriers of the R337H TP53 mutation. METHODS: The family histories of 30 kindreds of 41 southern Brazilian children with ACT were obtained. A PCR based assay was used to detect this P53 mutation in a large number of relatives of children with ACT. In all, 927 individuals were tested for the mutation, 232 from the non-carrier and 695 (including the 40 probands) from the carrier parental lines. RESULTS: 40 children with ACT carried the TP53 R337H mutation; the remaining child with ACT was not tested. There was no evidence of Li-Fraumeni syndrome in any of the kindreds; however, seven met the criteria for Li-Fraumeni-like syndrome. The carrier parental line was identified in each kindred. Of the 695 individuals tested in the carrier parental line, 240 (34.5%) were positive for the mutation, while none of the 232 individuals in the other parental line carried the mutation. The penetrance of ACT was 9.9% (95% confidence interval, 8.7% to 11.1%). CONCLUSIONS: The TP53 R337H mutation dramatically increases predisposition to childhood ACT but not to other cancers, and explains the increased frequency of ACT observed in this geographic region.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Penetrancia , Proteína p53 Supresora de Tumor/genética , Distribución por Edad , Niño , Preescolar , Femenino , Genotipo , Humanos , Lactante , Masculino , Linaje , Factores de Riesgo
15.
Leukemia ; 31(2): 333-339, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27560110

RESUMEN

To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during remission induction. MRD levels on day 19 predicted treatment outcome for patients with hyperdiploid >50 ALL, National Cancer Institute (NCI) standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL. Patients with t(12;21)/(ETV6-RUNX1) or hyperdiploidy >50 ALL had the best prognosis; those with a negative MRD on day 19 had a particularly low risk of relapse: 1.9% and 3.8%, respectively. Patients with NCI high-risk B-ALL or T-cell ALL had an inferior outcome; even with undetectable MRD on day 46, cumulative risk of relapse was 12.7% and 15.5%, respectively. Among patients with NCI standard-risk B-ALL, the outcome was intermediate overall but was poor if MRD was ⩾1% on day 19 or MRD was detectable at any level on day 46. Our results indicate that the clinical impact of MRD on treatment outcome in childhood ALL varies considerably according to leukemia subtype and time of measurement.


Asunto(s)
Neoplasia Residual/patología , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Recurrencia , Inducción de Remisión , Análisis de Supervivencia , Resultado del Tratamiento
16.
Clin Pharmacol Ther ; 101(3): 373-381, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27564568

RESUMEN

We performed a genomewide association study (GWAS) of primary erythrocyte thiopurine S-methyltransferase (TPMT) activity in children with leukemia (n = 1,026). Adjusting for age and ancestry, TPMT was the only gene that reached genomewide significance (top hit rs1142345 or 719A>G; P = 8.6 × 10-61 ). Additional genetic variants (in addition to the three single-nucleotide polymorphisms [SNPs], rs1800462, rs1800460, and rs1142345, defining TPMT clinical genotype) did not significantly improve classification accuracy for TPMT phenotype. Clinical mercaptopurine tolerability in 839 patients was related to TPMT clinical genotype (P = 2.4 × 10-11 ). Using 177 lymphoblastoid cell lines (LCLs), there were 251 SNPs ranked higher than the top TPMT SNP (rs1142345; P = 6.8 × 10-5 ), revealing a limitation of LCLs for pharmacogenomic discovery. In a GWAS, TPMT activity in patients behaves as a monogenic trait, further bolstering the utility of TPMT genetic testing in the clinic.


Asunto(s)
Antimetabolitos Antineoplásicos/farmacocinética , Leucemia/tratamiento farmacológico , Mercaptopurina/farmacocinética , Metiltransferasas/genética , Antimetabolitos Antineoplásicos/administración & dosificación , Niño , Relación Dosis-Respuesta a Droga , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Mercaptopurina/administración & dosificación , Farmacogenética , Polimorfismo de Nucleótido Simple
17.
Circ Res ; 89(7): 591-8, 2001 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-11577024

RESUMEN

Physiological and pathological cardiac hypertrophy have directionally opposite changes in transcription of thyroid hormone (TH)-responsive genes, including alpha- and beta-myosin heavy chain (MyHC) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), and TH treatment can reverse molecular and functional abnormalities in pathological hypertrophy, such as pressure overload. These findings suggest relative hypothyroidism in pathological hypertrophy, but serum levels of TH are usually normal. We studied the regulation of TH receptors (TRs) beta1, alpha1, and alpha2 in pathological and physiological rat cardiac hypertrophy models with hypothyroid- and hyperthyroid-like changes in the TH target genes, alpha- and beta-MyHC and SERCA. All 3 TR subtypes in myocytes were downregulated in 2 hypertrophy models with a hypothyroid-like mRNA phenotype, phenylephrine in culture and pressure overload in vivo. Myocyte TRbeta1 was upregulated in models with a hyperthyroid-like phenotype, TH (triiodothyronine, T3), in culture and exercise in vivo. In myocyte culture, TR overexpression, or excess T3, reversed the effects of phenylephrine on TH-responsive mRNAs and promoters. In addition, TR cotransfection and treatment with the TRbeta1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1, and TRalpha1 to alpha-MyHC transcription and increased myocyte size. We conclude that TR isoforms have distinct regulation and function in rat cardiac myocytes. Changes in myocyte TR levels can explain in part the characteristic molecular phenotypes in physiological and pathological cardiac hypertrophy.


Asunto(s)
Cardiomegalia/fisiopatología , Regulación de la Expresión Génica , Miocardio/metabolismo , Receptores de Hormona Tiroidea/genética , Receptores de Hormona Tiroidea/metabolismo , Animales , ATPasas Transportadoras de Calcio/genética , ATPasas Transportadoras de Calcio/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Actividad Motora , Miocardio/citología , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Fenotipo , Fenilefrina/farmacología , Condicionamiento Físico Animal , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Hormona Tiroidea/agonistas , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico , Transfección , Triyodotironina/farmacología
18.
Eur J Clin Nutr ; 60(11): 1311-6, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16775584

RESUMEN

OBJECTIVE: To evaluate the educational influence in the relative validation of a semiquantitative food frequency questionnaire (FFQs) for adults in the city of Viçosa, Brazil. DESIGN AND SUBJECTS: Four 24-h dietary recalls (reference method) were applied to a sample of 94 adults of both genders, at intervals of 1 month. At the end of the study, an FFQs consisting of 58 food items was also applied. Then, the individuals were divided into two main groups according to their educational level (lower and higher). The dietary data were calculated by the Diet Pro 4.0 software and analyzed according to differences of means or medians and Pearson's correlation coefficients. These coefficients were adjusted by the energy and corrected by the within-person variance for each educational group, considering the extreme quartiles of the data distribution. RESULTS: The intake of energy and nutrients, based on the 24 h dietary recalls, was inferior for the lower educational group (P < 0.05). For the FFQs, just the protein and calcium intakes were statistically different, suggesting interference of the education variable in this assessment. Over estimations in the FFQs were identified in the analyses of means and medians for vitamin C and retinol intakes in the lower education group and for retinol in the higher education one. However, when evaluated by correlation coefficients non-adjusted and adjusted, they were well correlated. On the other hand, lipid (r = 0.34) and calcium (r = 0.13) coefficients of the group with less instruction showed beneath the desirable values, suggesting weak consistence of the estimates provided by the FFQs for these nutrients. Correlation means of r = 0.65 and 0.54 were found for the higher and lower educational groups, respectively. CONCLUSIONS: The results indicate that FFQs showed acceptable performance on evaluating the habitual food consumption for most of the nutrients in the studied population. A tendency for better quantifications in the groups with higher education was observed, inferring its influence in the assessment of the dietary intake.


Asunto(s)
Dieta , Escolaridad , Evaluación Nutricional , Encuestas y Cuestionarios/normas , Adulto , Brasil , Ingestión de Energía , Femenino , Humanos , Masculino , Recuerdo Mental , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
19.
Leukemia ; 19(12): 2125-9, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16281077

RESUMEN

Despite substantial progress in the management of childhood acute myeloid leukemia (AML), only about 50% of patients are cured by intensive chemotherapy. The long-term results of clinical trials may reveal principles that can guide the development of future therapy. From 1980 to 2000, 251 patients <15 years of age with newly diagnosed AML were enrolled on one of the five consecutive St Jude AML studies. The median age of the 128 boys and 123 girls was 6.2 years; 193 were white, 45 black, and 13 of other racial groups. With the exception of one protocol (AML-83), outcomes improved in general over the two decades. The estimated 5-year event-free survival (+/-s.e.) was 30.8+/-5.6% for AML-80; 11.1+/-4.3% for AML-83; 35.9+/-7.4% for AML-87; 43.5+/-6.2% for AML-91; and 45.0+/-11.1% for AML-97. Resistant or relapsed AML caused the great majority of treatment failures. Increasing the intensity of chemotherapy (AML-87) did not improve outcome, partially because of toxicity, nor did prolonging postremission therapy by adding sequential myeloablative (AML-80) or nonmyeloablative (AML-83) chemotherapy cycles. We conclude that subtype-specific therapies are needed to replace the 'one size fits all' strategy of the past two decades.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos Antineoplásicos/normas , Leucemia Mieloide/terapia , Enfermedad Aguda , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Leucemia Mieloide/mortalidad , Masculino , Inducción de Remisión/métodos , Análisis de Supervivencia , Insuficiencia del Tratamiento , Resultado del Tratamiento
20.
Leukemia ; 19(8): 1399-403, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15973454

RESUMEN

To assess the prognosis of overt testicular disease at diagnosis of acute lymphoblastic leukemia, and any therapeutic role of irradiation for this involvement, we reviewed the data of 811 boys treated on St Jude studies Total X--XI (early period) and Total XII-XIV (recent period). In all, 19 boys (2.3%) had testicular disease at diagnosis. In the early period, patients with testicular leukemia had a poorer overall survival (OS) (P=0.003), event-free survival (EFS) (P=0.064), and higher cumulative incidence of relapse (P=0.041) than did other patients. During the recent period, patients with and without overt testicular leukemia did not differ in OS (P=0.257), EFS (P=0.102), or cumulative incidence of relapse (P=0.51). In a multivariate analysis, OS was lower for patients with testicular disease than for those without the involvement in the early period (P=0.047) but not in the recent one (P=0.75). Both patients who received irradiation for residual testicular disease at the end of induction subsequently died of leukemia. Of the other 17 patients who did not receive irradiation, only one developed testicular relapse in combination with bone marrow relapse. In conclusion, the prognostic impact of overt testicular disease has diminished. Irradiation appears to provide no survival advantage to this patient population.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Neoplasias Testiculares/radioterapia , Adolescente , Niño , Preescolar , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/terapia
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